E2- Summary Flashcards
What is a “trophic” hormone
Hormone that regulates hormone secretion by another gland
What type of hormone regulates processes in neighboring cells?
Paracrine
What type of hormone regulates processes within the cell of origin without being secreted?
Intracrine
What type of hormone “acts back” to regulate processes within the cell of origin?
Autocrine
What type of hormone originates in the neuron, and after axonal transport, is carried distally either by a blood vessel or synaptic transmission?
Neurocrine
What type of hormones are derived from amino acids and account for the majority of hormones?
Peptide hormones
What type of hormones are derived from tyrosine and come from the adrenal medullae and thyroid gland?
Amine hormones
What type of hormones are derived from cholesterol and have a cyclopentanoperhydrophenanthrene ring?
Steroid hormones
Follicle stimulating hormone Thyroid stimulating hormone Luteinizing hormone (LH) Human chorionic gonadotropin (hCG) Are apart of what class of hormones?
Glycoproteins (peptide family)
Aldosterone Cortisol Estradiol Progesterone Estrogen Testosterone DHEA Vitamin D Are apart of what class of hormones?
Steroids
Epinephrine Norepinephrine Dopamine Thyroxine (T4) Triiodothyronine (T3) Are apart of what class of hormones?
Amines
What classes of hormones are hydrophilic and are transported dissolved in the blood stream?
Peptides and catecholamines
What classes of hormones are hydrophobic and are transported bound to binding proteins?
Thyroid and steroids
What is the precursor for peptide hormones?
Specific genes that direct mRNA
Are peptide hormones stored?
Yes, in granules
What is the precursor for catecholamines?
Tyrosine
Are catecholamines stored?
Yes, in granules
What is the precursor for thyroid hormones?
Tyrosine and iodine
Are thyroid hormones stores?
Yes, in follicular cells
What is the precursor of steroids?
Cholesterol
Are steroid hormones stored?
No
Synthesis of peptide hormones
The gene for a hormone is transcribed into a mRNA in what part of the cell?
Nucleus
Synthesis of peptide hormones
The mRNA binds amino acids into a peptide chain called a preprohormone in what part of the cell?
Endoplasmic reticulum
Synthesis of peptide hormones
The preprohormone is cleaved into a prohormone in what part of the cell?
Endoplasmic reticulum
Synthesis of peptide hormones
The prohormone is cleaved to become the hormone is what part of the cell?
Golgi apparatus
What type of hormones may undergo peripheral tissue conversion to increase their biologic activity or to change their class?
Steroids and amines
In the skin, the prohormone vitamin D3 is converted to what?
1,25-dihydroxyvitamin D3
In the testes, the prohormone testosterone is converted into what?
Dihydrotestosterone (DTH) or estradiol
In the thyroid, the prohormone thyroxine (T4) is converted into what?
Triiodothyronine (T3)
What type of hormone secretion mechanism is activated by blood born substrates above or below the set-point?
Humoral
What type of hormone secretion mechanism is an extension of the CNS that signals to the gland to secrete the hormone?
Neural
What type of hormone secretion mechanism relies on hypothalamic factors to stimulate the pituitary gland to secrete TSH, which then stimulates the endocrine gland to secrete thyroid hormone?
Hormonal
What are to hormones that have positive feedback regulation?
Estrogen and Oxytocin
What type of hormones bind to receptors/channels located on the outer cell membrane of the target cell?
Hydrophilic hormones
Peptides and catecholamines
What type of hormones diffuse through the lipid bilayer and bind to a nuclear receptor in the target cell?
Hydrophobic hormones
Steroids and thyroids
What can occur when hormone levels are too high to reduce the physiologic response of hormones?
Decrease in maximal response (increasing the hormone does not increase the max response)
Decrease in sensitivity (more hormone is requires to produce 50% of the max response)
Where are magnocellular neurons of the hypothalamus primarily located?
Paraventricular (PVN) and Supraoptic nuclei (SON)
Where do magnocellular neurons terminate? What hormones do they release?
Posterior pituitary
Oxytocin, ADH/AVP, neurophysin
What acts as the neruovascular link between the hypothalamus and the anterior pituitary?
Parvicellular neurons
Where do parvicellular neurons terminate? What hormones do they release?
Median eminence
CRH, TRH, GnRH, GHRH, SS, DA
Once parvicellular neurons release their hormones in the median eminence, the hormones flow down the pituitary stalk in the _______ to the ______ lobe of the pituitary.
Hypothalmo-hypophyseal portal vessels
Anterior
Hormones from the parivicellular neurons regulate the secretion of what hormones from the anterior pituitary?
ACTH, GH, TSH, prolactin, LH, FSH
Somatostatin decreases the synthesis of what hormones?
GH and TSH
Thyroid releasing hormone (TRH) stimulates the release of what hormone from the pituitary?
What effect does this hormone have in mammary glands?
Prolactin
Breast development
Milk production
Gonadotropin releasing hormone (GnRH) stimulates the release of what hormones from the pituitary?
LH
FSH
What effect does LH have in gonads?
Females: ovulation and synthesis of estrogen
Males: secretion of testosterone from leydig cells
What effect does FSH have in gonads?
Females: development of follicle
Males; initiates spermatogenesis
Corticotropin releasing hormone (CRH) stimulates the release of what hormone from the pituitary?
What effect does this hormone have in adrenal glands?
ACTH
Growth of the adrenal gland and synthesis of corticosteroids
Prolactin releasing factor (PRF) stimulates the release of what hormone from the pituitary?
What effect does this hormone have in mammary glands?
Prolactin
Breast development
Milk production
Prepro-oxyphysin is cleaved into ____ in the hypothalamus.
Pro-oxyphysin
Pro-oxyphysin is cleaved into ____ and ____ in the axon.
Oxytocin and Neurophysin I
Neurophysin I arranges into tetramers that bind ____ preventing it from diffusing out of the axon in the posterior pituitary.
Oxytocin
Prepro-pressophysin is cleaved into ____ in the hypothalamus.
Pro-pressophysin
Pro-pressophysin is cleaved into ____ and ____ in the axon.
ADH/AVP and Neurophysin II
Neurophysin II arranges into tetramers that bind ____ preventing it from diffusing out of the axon in the posterior pituitary.
ADH/AVP
AVP/ADH is released following an increase in what?
Plasma osmolarity (dehydration) Osmoreceptors have direct contact with systemic circulation
Does release of AVP/ADH or thirst occur first?
Release of AVP/ADH
Does the osmoreceptor for magnocellular neurons have high or low sensitivity?
High
1% increase increase in osmolarity above the threshold produces an increase in ADP/AVP release
What are the overall homeostatic adjustments to dehydration?
AVP/ADH secretion
Water reabsorption (distal tubule, collecting duct)
Decreased urine output
Simulation of thirst
AVP/ADH is released following a decrease in what?
Blood volume or pressure
Decrease in BP decreases the stretch of baroreceptors and decreases their rate of firing
How does a decrease in the stretch of baroreceptors affect ADH/AVP?
Removes inhibition of AHD/AVP release, leading to an increase in ADH/AVP from magnocellular neurons
Baroreceptors also stimulate thirst centers
Decrease in BP is also perceived by the macula densa –> renin release
Does the stretch baroreceptor mechanism for magnocellular neurons have high or low sensitivity?
Lower sensitivity than the ADH/AVP system for osmolarity
8-10% decrease in blood volume/pressure below the threshold produces an increase in ADH/AVP release
Distention of the cervix, contraction of the uterus during parturition, or suckling of the nipple of the lactating breast transmit signals to the ___ and ___ where they provide ____ feedback for ____ release.
PVN and SON
Positive
Oxytocin
In addition to milk synthesis, suckling on a lactating breast, causes oxytocin to promote what?
Uterine regression
In a pregnant uterus, oxytocin causes what?
Rhythmic smooth muscle contractions to induce labor
The effects of oxytocin in the uterus are amplified by what?
An increase in receptors in uterine muscle
Increased gap junction formation between smooth muscle cells
The increase in oxytocin receptors in the uterus is mediated by what 2 hormones?
Oxytocin and progesterone
In the heart, oxytocin causes _____ release from ____.
ANP/BNP
Cardiomyocytes
Activation of peripheral aortic baroreceptors in response to stimuli (blood volume expansion, HTN) and integration within the nucleus tractus solitarius (NST) results in activation of what?
Oxytocin neurons (OTn)
What enhances the effect of oxytocin induced NO-dependent vasodilation?
Estrogen
What is the effect of oxytocin in the brain?
Decrease CRF (decreased cortisiol)
What is the effect of oxytocin in the heart?
Stimulates ANP release, which stimulates NO release from vascular endothelium to cause vasodilation to decrease BP
What is the effect of oxytocin in the kidney?
Increase urine output (increase diuresis)
Decrease aldosterone and renin production to cause vasodilation to decrease BP
In pre-diabetes, studies show that oxytocin increases peripheral glucose uptake via what?
GLUT4
What cell types are in the seminiferous tubules in the testes?
Germ cells
Sertoli cells
What cell types are in the connective tissue in the testes?
Leydig cells
What is the function of germ cells and sertoli cells in the seminiferous tubules in the testes?
Spermatogenesis
What is the function of leydig cells in the connective tissue in the testes?
Secrete testosterone
At puberty, some spermatogonia undergo ___ division to become _____.
Mitotic
primary spermatocytes
Each primary spermatocyte enters the _____ to become 2 secondary spermatocytes.
1st meiotic division
Each secondary spermatocyte enters the 2nd meiotic division to become what?
Spermatids
Developing sperm cells do not complete ____ during meiosis, therefore the 4 daughter cells form a _____.
Cytokinesis
Synctium
What ensures that haploid cells that contain either an X or Y chromosome, have access to all the gene products available in a complete diploid genome?
Synctium
Further maturation of the spermatids in the seminiferous tubule lumen creates what?
Spermatozoa
Which is the correct order of spermatogenesis?
- Spermatogonium –> Spermatogonia –> Primary spermatocyte –> Secondary spermatocyte –> Spermatids –> Spermatozoa
- Spermatozoa –> Spermatogonium –> Primary spermatocyte –> Secondary spermatocyte –> Spermatids –> Spermatogonia
- Spermatogonium –> Spermatogonia –> Primary spermatocyte –> Secondary spermatocyte –> Spermatids –> Spermatozoa
What establishes a blood-testes barrier, prevents immune cells from accessing genetically variant spermatoza and is needed for fertility?
Tight junctions between sertoli cells
What allows Y-sperm to transport necessary gene products to X-sperm?
Cytoplasmic bridges
What is the process by which spermatids are packaged and mature into spermatozoa?
Spermiogenesis
What is the process by which mature sperm are extruded from sertoli cells into the lumen of the seminiferous tubules?
Spermiation
Sperm pass through the ____ before entering the ______, the site for maturation
Rete testes
Epididymis
Pulsatile release of GnRH from the anterior pituitary stimulates the release of what two hormones?
FSH and LH
FSH stimulation in the testes causes the release of what?
Androgen-binding protein and inhibin release from sertoli cells
What is the function of inhibin in regards to hormone control of spermatogensis?
Negative feedback to FSH
What is the function of LH in the testes?
Promotes testosterone release from leydig cells
What is the function of testosterone in regards to hormone control of spermatogensis?
Negative feedback to FSH and LH
Testosterone can be converted to dihydrotestosterone (DTH) via what enzyme?
5a-reductase
Testosterone can be converted to estradiol via what enzyme?
Aromatase
Testosterone can be concentrated in the seminiferous tubules by binding to what?
Testosterone travels through the circulation bound to what?
Testosterone can be concentrated in the seminiferous tubules by binding to ABP
Testosterone travels through the circulation bound to sex-hormone binding globulin (SHBG)
Optimal spermatogenesis requires the action of ____ and ____ and the presence of adequate _____ cells.
Testosterone and FSH
sertoli cells
Differentiation of epididymis, vas deferens, and seminal vesicles Increased muscle mass Pubertal growth spurt Growth of penis seminal vesicles Deepening of voice Negative feedback on anterior pituitary Libio Are affects of what hormone?
Testosterone
Differentiation of penis, scrotum, and prostate Male hair pattern Sebaceous gland activity Growth of prostate Are affects of what hormone?
Dihydrotestosterone
*DTH is twice as potent as testosterone
What determines the rate of the spermatogenic cycle?
Rate is constant
Retinoic acid signaling within sertoli cells
(NOT accelerated by testosterone)
What determines the ultimate spermatogenic potential of the testes?
The number of sertoli cells that occur in development (sertoli cells cease proliferation at the end of puberty)
What is smaller than normal testicle size that results in low sperm counts?
Hypogonadism
What are some environmental factors that can cause oligozoospermia (< 15 million sperm/ml)?
Pollution
X-rays
Tobacco, alcohol, steroid use
Stress
What is the most widespread environmental factor producing oligozoospermia?
Interference with the ability of the scrotum to cool testes
What is undescended testes that are unable to produce viable sperm?
Cryptorchidism
What affect does marijuana have on sperm count?
Endocannabinoid receptors are present in the sperm and in the HPG axis
Decrease sperm count, alters morphology, and reduces activity
Suppressive effect of male sex hormones
What are 3 endocrine consequences to testosterone replacement therapy?
Reductions in LH and FSH through negative feedback
Reduced sperm production
Increase in free estrogen
What stimulates pubic and axial hair growth in men?
Dehydroepiandrosterone (DHEA)
Hair follicle miniaturation occurs with 5a-reductase conversion of testosterone to what?
What can be used to treat this?
DHT
Propecia (5a-reductase antagonist)
Can cause ED, loss of libido, reduced ejaculate
What produces 60% of the ejaculate while also adding fructose to nourish the sperm, prostaglandins to stimulate contractions in the reproductive tract, and clotting factors?
Seminal vesicles
What produces 20% of the ejaculate while also secreting alkaline fluid to counter the acidic vaginal environment and activate clotting factors?
Prostate
What produces 10% of the ejaculate while also adding lubrication fluid?
Bulburethral glands
What 2 physiologic responses allow for an erection?
Relaxation of the helicine arteries byEm NO to allow blood flow into cavernous spaces
Compression of the subtunical venules to decrease the venous return from the cavernous space
Upon sexual stimulation, the penis arterioles dilate by parasympathetic release of what?
NO
In the process of achieving an erection, the parasympathetic release of NO leads to the production of ___, thus lowering the intracellular Ca which promotes ___.
cGMP
Relaxation (allowing for increased blood flow)
What is the integration site for the CNS control of erections?
Medial Preoptic Area (MPOA)
The MPOA receives sensory input from the amygdala and sends impulses to where?
Paraventricular nuclei
Periaqueductal gray matter in the sacral spinal cord
Tonic ____ stimulation results in a flaccid penis
Sympathetic
In the flaccid state, blood flow into the penile tissue is limited by the contraction of what?
Helicine arteries and trabecular smooth muscle
Ejaculatory emission occurs from SNS impulses from ___ and ___
L1 and L2
What is the pathway of semen expulsion?
Seminiferous tubules —> Retes testes —> Epididymis—> Vas deferens –> ampulla –> urethra
What occurs as a result of failure of the urethral sphincter, allowing the semen into the bladder?
Retrograde ejaculation
What can be used to treat ED? How do they work?
What is a SE?
Phosphodiesterase inhibitors (PDE5)
“-afils”
Prevent cGMP degradation, leading to sustained NO levels
Activates PDE6 in the retina leading to vision changes
How does a vasectomy work?
Vas deferens are cut
Sperm can no longer move through the ejaculatory tract
Sperm removed through phagocytosis
Oogonia (2N) divide via ___into ___.
When does this occur?
Primary oocytes (2N)
Mitosis
Birth
Primary oocytes are arrested in what phase?
Until when?
Arrested in prophase I of meiosis until just before ovulation
In the follicular phase, ____ cells secrete a gel like substance that covers the oocyte called the _____.
Granulosa
Zona pellucida
In the follicular phase, cuboidal ____ cells proliferate from ___ stimulation and outer most layers become stratified. The surrounding ovarian tissue differentiates into ____ cells.
Granulosa FSH Thecal cells Inner cells = granulosa Outer cells = theca cells
In the follicular phase, ___ stimulation causes thecal cells to convert cholesterol to ___ via cholesterol desmolase
LH
Androstenedione (androgens)
In the follicular phase, LH stimulation causes ___ cells to convert ___ to androstenedione (androgens) via ___
Thecal
Cholesterol
Cholesterol desmolase
In the follicular phase, the androgens produced in the thecal cells diffuse into the ___ cells where upon ___ stimulation, they are converted to estradiol/estrogen via aromatase.
Granulosa
FSH
In the follicular phase, the androgens produced in the thecal cells diffuse into the granulosa cells where upon FSH stimulation, they are converted to ___ via ___.
Estradiol/estrogen via aromatase.
In the follicular phase, some of the estrogen produced by the granulosa cells is secreted into the blood and binds to proteins, but some remains in the follicle to contribute to what?
Antral formation
In the follicular phase, one follicle usually grows more rapidly and matures about 14 days after onset of follicular development and is called what?
This follicle contain a ___ oocyte which has completed ____.
Graafian follicle
Secondary oocyte (N)
Meiosis I
(this occurs just before ovulation)
The Graafian follicle ruptures by enzymatic digestion to release the oocyte, what is this event called?
Ovulation
The released oocyte enters the ___ where it may or may not be fertilized.
Oviduct
In the luteal phase, old follicular cells undergo structural transformation to form what?
Corpus luteum
In the luteal phase, luteal cells enlarge and become ___ hormone producing tissues.
What is a nickname of the corpus luteum?
Cholesterol
“yellow body” due to storage of cholesterol
In the luteal phase, if released oocyte is not fertilized and does not implant, corpus luteum degenerates within about 14 days and becomes what?
What is nick name of this structure?
Corpus albicans
“white body” due to fibrous tissue
In the luteal phase, if fertilization and implantation do occur, the corpus luteum continues to grow and produce ___ and ___ and becomes the corpus luteum of pregnancy.. Sperm entry triggers what?
Estrogen and progesterone
Meiosis II
In the luteal phase, theca and granulosa cells only secrete ___ after being converted into luteal cells
Progesterone
GnRH is released in a pulsatile manner.
What gonadotrope is stimulated by a low pulse frequency of GnRH?
What gonadotrope is stimulated by a high pulse frequency of GnRH?
Low = FSH High = LH
What are the 3 main functions of FSH in the follicular phase?
Stimulate proliferation of cuboidal granulosa cells
Stimulate granulosa cells to convert androgens to estrogen via aromatase
Induce inhibin release from ganulosa cells for negative feedback of FSH
In the follicular phase what hormone has negative feedback on gonadotropes in general (FSH/LH)?
Estrogen
Th high amounts of estrogen from FSH signaling in the follicular phase causes what?
Estrogen to have positive feedback
What does estrogen positive feedback cause?
LH surge (FSH does not rise as much due to inhibin)
What are the effects of the LH surge? (5)
- Conversion of antral follicle to Graafian follicle
- Meiosis is resumed
- Production of proteolytic enzymes in follicle (digest follicle for ovulatory rupture)
- Increase prostaglandins
- Differentiates follicle cells into corpus luteum
In the luteal phase, what hormone has negative feedback on the hypothalamus and pituitary, which suppresses the positive feedback of estrogen, therefore suppressing a second LH surge?
Progesterone
What phase of the endometrial cycle occurs on days 0-4 and
discharges blood and endometrial debris from vagina?
Menstral phase
Menses occurs __ days after ovulation, regardless of cycle length.
Therefore, cycles longer than 28 days have a longer ___ phase.
14
Proliferative (follicular)
The menstrual phase of the endometrial cycle coincides with what phase of the ovarian cycle?
The end of ovarian luteal phase and onset of follicular phase
The release of what hormone causes vasoconstriction of endometrial vessels which disrupts blood supply and results in the death of the endometrium?
Prostaglandins
The release of what hormone stimulates mild rhythmic contractions of uterine myometrium which helps expel blood and endometrial debris from the uterine cavity to the vagina?
Prostaglandins
What phase of the endometrial cycle occurs on days 5-14?
Proliferative phase
The proliferative phase of the endometrial cycle begins concurrently with what part of the ovarian cycle?
Last portion of the ovarian follicular phase
In the proliferative phase of the endometrial cycle, the endometrium starts to repair itself and proliferates under the influence of ____ from newly growing follicles.
Estrogen
What phase of the endometrial cycle lasts from the end of menstruation to ovulation?
Estrogen-dominant proliferative phase
What phase of the endometrial cycle occurs on days 15-28?
Secretory phase
What phase of the endometrial cycle does the uterus enter after ovulation when the corpus luteum is formed?
Secretory phase
Secretory phase of the endometrial cycle, progesterone from the corpus luteum converts the endometrium into what?
A highly vascularized, glycogen-filled tissue
What hormone is responsible for the growth and development of the vagina, uterus, and oviducts?
Estrogen
What is the effect of estrogen in the fallopian tubes?
Increases the number of cilia and their rate of beating, drawing the ovum into the tube
What is the effect of estrogen in the myometrium of the uterus?
Increases oxytocin receptors and contractions
What is the effect of estrogen in the endometrium of the uterus?
Thickens, increases permeability, and blood supply
*Synthesizes receptors for progesterone on uterine cells
What is the effect of estrogen in the cervix?
Makes mucous thin, watery, and alkaline
Increases distensibility, making birth easier
What is the effect of estrogen in the vagina?
Proliferation of epithelial layer
Increases vaginal secretions
What is the effect of estrogen in the mammary glands?
Increases ductal growth and growth of the breast
Increases nipple size and pigmentation
What is the effect of estrogen in the body?
Increased deposit of subcutaneous fat (hips/breasts)
What is the effect of estrogen in the skeletal system/Ca metabolism?
Epiphyseal closure
Calcium uptake into bone
What is the effect of estrogen in the skin?
Inhibits body and facial hair growth (except pubic and axillary)
Promotes pubic and axially hair growth
What is the effect of estrogen in the kidney?
Increases absorption of Na, Cl, and H2O
Contributes to bloating during menstrual cycle
What is the effect of estrogen in the heart?
Maintains low blood cholesterol
Arterial vasodilator
Decreases atherosclerosis
What hormone is responsible for implantation of the zygote and the maintenance of the pregnant state?
Progesterone
What is the effect of progesterone in the uterus?
*Needs estrogen prior to stimulation
Converts uterus into an actively secreting tissue
Induces decidua formation (placenta)
Decreases contractility
What is the effect of progesterone in the cervix?
Decreases distensibility
Makes mucous thick and acidic
What is the effect of progesterone in the vagina?
Decreases proliferation of epithelium layer
What is the effect of progesterone in the mammary glands?
Increases branching of the ductal system
Stimulates development of lobules and alveoli
What is the effect of progesterone in the body?
Increases temperature following ovulation (indication that ovulation has occurred)
Increases appetite
What is the effect of progesterone in the kidney?
Decreases Na reabsorption by competing with aldosterone
What causes menstrual cramps?
What is severe pain combined with nausea, vomiting, and diarrhea called?
Contraction of the uterus caused by increased prostaglandins
Dysmenorrhea
What phase of the ovarian cycle is PMS associated with?
Luteal phase
What is defined by a decline in fertility associated with a decline in ovarian function, FSH > 30 mlU/mL and no menses for 12 mo in women of typical age range?
Menopause
In the first step of menopause, there is a decrease in the follicle pool which leads to what?
Decreased Inhibin –> Increased FSH –> Acceleration of follicular maturation –> Shorter cycle
In the second step of menopause there is a further decrease in the follicular pool which leads to what?
Decreased estrogen –> Delayed positive feedback –> Longer cycle
Insufficient estrogen –> No positive feedback –> Anovulatory
In the third step of menopause there is a lack of estrogen which leads to what?
Increased LH and FSH
Cycle arrest
Hot flashes Urogenital atrophy Cognitive function Increased risk of Alzheimer’s disease Osteoporosis Cardiovascular disease Are all what?
Clinical concerns of menopause
How does a tubectomy work?
Fallopian tubes are cut
Prevents eggs from reaching the uterus for fertilization
What is the MOA of hormonal contraceptives?
Prevents ovulation by negative feedback on the anterior pituitary, preventing LH surge
The combination of sex chromosomes at the time of conception determined what?
Genetic sex
Whether testes or ovaries develop and the presence or absence of a Y chromosome determines what?
Gonadal sex
The presence or absence of masculinizing hormones and the apparent anatomic sex determines what?
Phenotypic sex
The sex-determining region of the Y chromosome (SRY) codes for the production of what?
Testis-determining factor (TDF)
Testis-determining factor (TDF) directs the differentiation of gonads into what?
Testes
Testes secrete ___ from leydig cells and ___ from sertoli cells.
Testosterone from leydig cells
Mullerian-inhibiting factor from sertoli cells
Mullerian-inhibiting factor causes secreted from the sertoli cells, causes what?
Degeneration of Mullerian ducts
Testosterone secreted from leydig cells is converted to dihydrotestosterone (DTH) via what?
5-a reductase
DTH promotes the development of undifferentiated external genitalia into what?
Male external genitalia (penis, scrotum)
The absence of what causes the development of female external genitalia?
DTH
Testosterone secreted from leydig cells transforms what into male reproductive tract (epididymis, ductus deferens, ejaculatory duct, seminal vesicles)?
Wolffian ducts
What is required what ovarian development?
Two functional X chromosomes
After an embryo has been made with 2 functional XX chromosomes, what is the next step in sexual differentiation?
There is no Y chromosome present, so there is no SRY gene to code for TDF
With no TDF, undifferentiated gonads develop into ovaries
(hormone independent process)
In the process of female sex differentiation, there is no development of testes and therefore no secretion of what?
Testosterone (from Leydig cells)
Mullerian-inhibiting factor (from Sertoli cells)
In the process of female sex differentiation, the absence of testosterone leads to what?
Degeneration of Wolffian ducts
Development of female external genitalia (clitoris, labia)
(hormone independent process)
In the process of female sex differentiation, the absence of Mullerian-inhibiting factor leads to what?
Development of Mullerian ducts into female reproductive tract (oviducts, uterus)
(hormone independent process)
15 yr old girls presents with standard breast development, an appropriately timed growth spurt, and amenorrhea. She has female external genitalia with a shortened vagina that ends in a blind pouch w/o a cervix. There are bilateral inguinal masses. Testosterone: high DTH: normal FSH and inhibin: normal LH: high AMH: high Chromosome: 46 XY Biopsy: absence of binding affinity of testosterone to androgen receptors What is her dx?
Complete Androgen Insensitivity Syndrome
XY
Presence of testes
Secretion of AMH and testosterone
AMH causes degeneration of mullerian ducts
Loss of function of testosterone receptors cause the degeneration of the wolffian duct and the development of female external genitalia
What are the 3 testes cell types?
Germ cells (spermatogonia) Sertoli cells (produce antimullerian hormone) Leydig cells (produce testosterone)
What are the 3 ovary cell types?
Germ cells (oogonia) Granulosa cells (produce estradiol) Theca cells (produce androgens and progesterone)
XY Individuals lacking SRY gene are defined by what?
No gonads
Develop as female
XX individuals with SRY translocation are defined by what?
Testes
Develop as male
XY individuals with defective antimullerian hormone production or action are defined by what?
Testes
Both male and female internal reproductive tracts develop
Male external genitalia
Individuals with a 5-a reductase deficiency are defined by what?
Testes Male internal reproductive tract Female external genitalia Male pseudohemaphrotidism Large clitoris at birth that develops into a penis at puberty due to the increase in testosterone
When does puberty begin for boys?
When does puberty begin for girls?
8-13 for girls
9-14 for boys
What is characterized by maturation of the hypothalamic-pituitary-gonadal axis, appearance of secondary sex characteristics, acceleration of growth, and capacity for fertilization?
Puberty
There are transient peaks in gonadotropins (LH, FSH) during gestation and early infancy and then ___ levels in childhood
Low
After puberty, women develop monthly cyclic bursts, with __ concentrations exceeding __ concentrations.
LH>FSH
Both genders show increased gonadotropin production after 50 years of age, with __ exceeding __ levels.
FSH>LH
What marks the start of puberty in boys?
Increase in testicular size (gonadarche)
`At what age is sperm production and ejaculatory capability developed?
13.5-13.7 years old
What marks the start of puberty in girls?
Thelarche (breast development)
At what age does menarche usually occur? What is unique about the first few cycles?
By age 13
No ovulation for the first few cycles because there is no positive feedback by estrogen
What hormone promotes epiphyseal fusion in both genders?
Estrogen
Longer time to reach puberty accounts for most of the difference in stature
What hypothesis suggest that puberty timing is based on the reduction in intrinsic suppression of GnRH, leading to reactivation of gonadotropin synthesis and secretion?
Hypothalamic Maturation hypothesis
What hypothesis suggest that puberty timing is based on decreased sensitivity to the negative feedback of estrogen (females) or testosterone (males), leading to reactivation of gonadotropin synthesis and secretion?
Gonadostat hypothesis
One factor that influences pubertal timing is the increase in pulsatile release of ___ leading to an increased ratio of___ that correlates with the onset of puberty
GnRH
LH/FSH
First occurs in sleep
What is leptin theory for pubertal timing?
A metabolic signal from adipose tissue may control onset of sexual maturation
Leptin (product of obese gene)
What is the melatonin theory for pubertal timing?
Melatonin inhibits GnRH release
Melanin is secreted from the pineal gland, so puberty may be initiated by a reduction in melatonin secretion with the removal of the pineal gland that precipitates puberty
What is defined as the development of secondary sexual characteristics before age 8 in boys or age 9 in girls?
Precocious puberty
What is seen with Gonadotropin-dependent precocious puberty?
Increased gonadotropins (LH, FSH)
Increased gonadal hormones (estrogen, testosterone)
CNS tumors
What is seen with Gonadotropin-independent precocious puberty?
Normal gonadotropins (LH, FSH) Increased gonadal hormones (estrogen, testosterone)
What is defined as the lack of physical maturation 2 SD beyond the mean onset?
Delayed puberty
17 year old boy with no physical signs of puberty presents with deficiency of pulsatile release of gonadotropins from pituitary that results in low levels of gonadal hormones. He has no signs of anosmia and does not respond to a GnRH injection
What do you suspect?
Idiopathic Hypogonadotropic Hypogonadism
low gonadotropins (LH, FSH) result in low gonadal hormones
17 year old boy with no physical signs of puberty presents with deficiency of pulsatile release of gonadotropins from pituitary that results in low levels of gonadal hormones. He has signs of anosmia and responds to a GnRH injection
What do you suspect?
Kallman’s Syndrome
17 yr old girl presents with no signs of physical puberty and amenorrhea. PE shows female genital tract, but no functional gonads. What do you suspect?
Turner’s syndrome (XO)
Primary gonadal failure
What is the most common cause of primary testicular failure?
Klinefelter’s Syndrome (47, XXY)
What are 2 types of Hypergonadotropic Hypogonadism?
Turner’s Syndrome (XO)
Klinefelter’s Syndrome (47, XXY)
What are 2 types of Hypogonadotropic Hypogonadism?
Idiopathic Hypogonadotropic Hypogonadism
Kallman’s Syndrome
17 year old male patients presents with feminization and testicular failure due to lack of negative feedback. What do you suspect?
Klinefelter’s Syndrome (47, XXY)
low gonadal hormones (estrogen, testosterone) result in high gonadotropins (estrogen, testosterone
What are complications of Klinefelter’s Syndrome?
Germ cell tumors, breast cancer, osteoporosis
Where is the site of fertilization
Upper third of oviduct (ampulla)
What is released by mature eggs and acts a chemoattractant for sperm to reach egg in ampulla of oviduct?
Allurin
Sperm transport is assisted myometrial contractions, which are stimulated by what?
Prostaglandins in the ejaculate
Upon sperm passage through female reproductive tract, what occurs?
Capacitation (activation) occurs
What process gives the sperm the ability to fertilize eggs?
Capacitation
What three things occur in the process of Capacitation?
Cholesterol is withdrawn
Surface proteins are redistributed
Calcium influx
(Increases motility –>whiplashing)
Capacitated sperm penetrate the corona radiata and bind to ___ proteins on the ____.
ZP3 proteins
Zona pellucida
The binding of the sperm to the ZP3 proteins on the zona pellucida triggers what?
The acrosomal reaction
During the acrosomal reaction, ___ is released from the acrosome and digests the ___, creating a pathway to the plasma membrane of the ovum.
Acrosin (hydrolytic enzyme)
Zona pellucida
When the sperm reaches the ovum, the ___ of the 2 cells fuse.
Plasma membrane
The fusion of the sperm and ovum plasma membrane is mediated by what?
The binding of fertilin on the sperm head to an integrin receptor on the ovum’s membrane
The sperm stimulates release of enzymes stored in the ___ in the ovum, which in turn inactives ___ proteins and ___ the zona pellica.
What does this prevent?
ZP3 proteins
Cortical granules
Hardens
Polyspermy
What occurs after the completion of the zona reaction?
Signals ovum to complete the 2nd meiotic division
The fertilized ovum divides by ___. Within a week it grows into a ___ capable of implantation.
Mitosis
blastocyst
The blastocyst adheres to the endometrial lining and ___ cells penetrate the endothelium to accomplish implantation.
Cords of trophoblastic
Because of what hormone are days 20-24 of a regular 28 cycle are the optimal period for implantation?
Progesterone
hCG in maternal serum is only detectable after ___ is complete (8-11 days after conception)
Implantation
Placental hcG rescues what?
The corpus leuteum
What is responsible for:
Exchange between maternal and fetal blood
Performs the functions of the digestive system, the respiratory system, and they kidneys for the fetus
Prevents immunologic rejection
Acts as transient endocrine organ that secretes essential pregnancy hormones?
Placenta (operational 5 weeks after implantation)
What hormones the placenta secrete?
hCG
Estrogen
Progesterone
What maintains the corpus luteum until the placenta take over the last 2 trimesters?
hCG
When the placenta begins to secrete estrogen and progesterone, the hCG levels decline and the corpus luteum regresses
Does estrogen or progesterone synthesis require both the fetus and the placenta for synthesis?
Estrogen
In the synthesis of estrogen by the placenta, cholesterol (placenta) is converted to _____ (placenta), which then enters the fetus.
Pregnenolonen
In the synthesis of estrogen by the placenta, Pregnenolonen (fetus), is converted into ____ (fetus), via the fetal adrenal gland.
DHEA-sulfate
In the synthesis of estrogen by the placenta, DHEA-sulfate (fetus), is converted into ____ (fetus), via the fetal liver; which then enters the placenta.
16-OH DHEA-sulfate
In the synthesis of estrogen by the placenta, 16-OH DHEA-sulfate (mother), is converted to ____ (mother) via aromatase or sulfatase.
Estriol
What is the sequence of synthesis of estrogen by the placenta?
Cholesterol –> pregnenolone –>DHEA-sulfate –> 16-OH DHEA-sulfate –> Estriol
In the synthesis of progesterone by the placenta, cholesterol (mother), is converted to ____(mother).
Pregneolone
In the synthesis of progesterone by the placenta, pregneolone (mother), is converted to ____(mother).
Progesterone
What pregnancy hormone inhibits myometrial contractions and prostaglandin synthesis?
Progesterone
In the first 2 trimesters, the uterus is quiet due to progesterone.
In the last trimester, the uterus becomes progressively more excitable. What are these early contractions called?
Braxton-Hicks contractions`
What hormone produced by corpus luteum and the placenta, relaxes the pelvic ligaments and softens the cervix by loosening the connective tissue between pelvic bones?
Relaxin
What are the 3 roles of high estrogen levels in labor induction?
- Synthesis of connexons for gap junctions –> coordinated contraction
- Increase concentration of myometrial receptors for oxytocin –> increase responsiveness to oxytocin
- Increase production of prostaglandins –> cervical ripening and increase response to oxytocin
What causes the uterine responsiveness to oxytocin to be greater at term than in nonpregnant women?
Even though circulating blood levels of oxytocin remains constant, there is a profound effect of oxytocin at term due to the increased concentration of myometrial oxytocin receptors
What initiates labor?
Labor is initiated when the oxytocin receptor concentration reaches a critical threshold that permits the onset of strong, coordinated contractions
What is the role of Corticotrophin-releasing hormone (CRH) in labor induction?
- Fetal portion of placental secretes CRH into the fetal circulation, which results in increased fetal ACTH
- ACTH stimulates the fetal adrenal cortex to make DHEA and fetal cortisol
- DHEA –> estrogen
- Cortisol –> fetal lung maturation
What hormone acts as a placental clock for timing parturition?
Corticotrophin-releasing hormone (CRH)
High: premature delivery
Low: late delivery
Uterine stretching (especially with multiple pregnancies), increased production of macrophages from pulmonary surfactant, bacterial infection, and allergic reactions activates what in the uterus?
NF-kB (nuclear factor)
NF-kB (nuclear factor) stimulates the production of ___ and ___, which promote cervical softening.
Cytokines (IL-8) and prostaglandins
What positive-feedback cycle progressively increases until cervical dilation and delivery are complete?
Baby’s head stretches the cervix –> excites fundic contraction –> pushes baby down –> stretches the cervix
What is a pharmacologic synthetic form of oxytocin that can be used to induce labor?
Pitocin
Why does lactation not occur during pregnancy?
Inhibition from estrogen and progesterone
After parturition, estrogen and progesterone decrease, so lactation can occur
(they promote development of during gestation; Estrogen-ductal grown, Progesterone-lobules and alveoli)
What is the nervous pathway of the sucking reflex?
Posterior pituitary –> increase oxytocin –> contraction of myoepithelial cells surrounding alveoli –> milk ejection
(can be stimulated by infants cry/smell or inhibited by stress)
What is the prolactin pathway of the sucking reflex?
Anterior pituitary –> increase prolactin –> secretion by alveolar epithelial cells –> milk secretion/production
What 2 hormones control the release of prolactin?
Thyrotropin-relasing hormone (stimulatory)
Dopamine (inhibitory)
What hormone acts as a natural contraceptive during regular breast feeding? How?
Prolactin
Inhibits GnRh release preventing ovulation
28 year old female patient prevents with pelvic pain, heavy menses, and pain during intercourse. PE shows evidence of ovarian cysts and infertility. What do you suspect?
Endometriosis
28 year old female patient prevents with irregular heavy menses, dark coarse hair on her face and chest, persistence acne, and difficulty becoming pregnant.
US shows ovarian enlargement with 20 follicles.
Blood test shows elevated LH/FSH ratio and testosterone. What do you suspect?
Polycystic ovarian syndrome
(Stein-Leventhal Syndrome)
Irreggular/anovulation
Genetic predisposition to excess androgen secretion
Affected by dietary factors
Newborn girl presents with an enlarged clitoris.
PE: vagina and labial folds, no inguinal masses
US: ovaries and uterus, no testes
Blood tests: Elevated ACTH, 17-ketosteroid, and testosterone
Karyotype: 46XX
What do you suspect?
Congenital Adrenal Hyperplasia
21-hydroxylase deficiency (Virilized XX)
Most common cause of genital ambiguity and can lead to life-threating adrenal insufficiency within the first weeks of life
What is the pathophysiology behind Congenital Adrenal Hyperplasia/21-hydroxylase deficiency?
Reduced cortisol –> Increased ACTH –> adrenal hyperplasia –> increased progesterone precursors are converted to testosterone
Why would high testosterone decrease male fertility?
Testosterone inhibits the release of gonadotropins
