GEP (Life Cycle) Week 1 Flashcards
Identidy the anatomy of the Vulva
Clinical significance:
- Bartholin’s glands (greater vestibular glands)
- Located either side of the vaginal orifice
- Secrete lubricating mucus during sexual arousal
- Can become infected/inflamed or a cyst produced
Identify the anatomy of the Male Reproductive system Part 1
Identify the anatomy of the Male Reproductive system Part 2
Identidy the anatomy of the Inguinal Canal
● Passage in anterior abdominal wall
● Holds structures; differ depending
on sex (embryological feature)
● One on each side
● Begins at deep inguinal ring
● Ends at superficial inguinal ring
Borders of Inguinal Canal: MALT
M: muscles (roof)
A: aponeurosis (anterior wall) L: ligaments (floor)
T: tendon (posterior wall)
What are steroid hormones
Steroid hormones are a series of cholesterol derived hormones that are made in the cortex of the adrenal glands,
-They are classified as mineralocorticoids, glucocorticoids, sex hormones.
-Mineralocorticoids are made in the zona glomerulosa of the cortex
-Glucocorticoids are made in zona fasciculata in the cortex
-Sex hormones are made in the zona reticularis in the cortex, also produced in the gonads and the placenta
Steroids are lipid-soluble, so pass through target cell
membranes and bind to nuclear receptors in
cytoplasm. A hormone-receptor complex forms and
translocates to the nucleus.
These complexes act as transcription factor for target
genes which upregulate for a desired effect.
Describe the HPA axis of Cortisol
-Hypothalamus releases CRH which acts in the pituatiary glands which then releases ACTH. This ACTH acts on the adrenal gland releasing cortisol into the immune system and through negative feedback it is controlled.
Describe the HPG axis of sex steroids
-The hypothalamus releases GnRH which acts on the pituatiary gland
-The pituatiary gland then relases LH and FSH which act on the gonads.
-Female gonads (ovaries) release estradiol progesterone and the male gonads (testes) releases tesosterone.
-Unlike the HPA, the negative feedback system can act on both the pituatiary gland and hypothalamus.
GnHR is secreted in pulsatile fashion, fast pulses favour LSH and slow favour LH.
LH: luteinzing hormones
FSH: Follicle-stimulating hormones
What is steroidgenesis
This the processes by which cholesterol is converted to steroid hormones
How does Steroidgenesis occur and the different products
Cholesterol side-chain cleavage enzyme converts cholesterol (27C) → pregnenolone (21C), a progestogen.
Key points:
● 21-hydroxylase converts progestogens into
gluco-/mineralo-corticoids (21C)
● 2 more carbons are removed from
progestogens to make androgens (19C)
● 5 alpha-reductase converts testosterone
into dihydrotestosterone (DHT - a more
potent androgen)
● Oestrogens (18C) are produced from
androgens using the aromatase enzyme
● Oestrogens may be written as E1/2/3,
depending on number of -OH groups attached
What triggers Mineralcorticoid and what are its effect- Aldosterone
Triggers:
● Low BP - activate RAAS → angiotensin II
● Low Na+/high K+
● Stress - HPA axis stimulates aldosterone
Effects:
Binds to nuclear receptors in cells that line the DCT
and collecting ducts
Promotes the excretion of K+ and the retention of Na+ (eNaC). H2O follows Na+ through aquaporins, causing an increase in blood volume and BP.
[NB: K+ sparing diuretics (e.g.spironolactone) are antagonists of this system]
What triggers glucocorticoids and its effect- Cortisol
Triggers:
Remember from diabetes week that cortisol is a counter-regulatory hormone. These are released under conditions of A) chronic stress and B) hypoglycaemia
Once again, the HPA axis is the mechanism that controls cortisol release
Effects:
A) Cortisol increases sensitivity of alpha receptors of arteries, leading vasoconstriction → TPR increases → BP increases
B) Gluconeogenesis is promoted in the liver by increasing the availability of amino acids (from proteins) and fatty acids (from adipose tissue) for the production of glucose. Direct production from glycogen also occurs
What is excess cortisol known as and what does it cause
Known as cushings syndrome
What are the 2 main androgens that are converted into tesosterone in the testes
Androstenedione and dihydroepiandrosterone (DHEA) are both androgens that are converted into testosterone in the testes
Both hormones increase during puberty and control associated changes
What happens in female to produce androgens
In females, androgens are converted into oestrogens in the ovaries
hormones increase during puberty and control associated changes
What are the effects of androgen and oestrogen
Androgens - increased libido, sebaceous secretions, appearance of pubic/facial/axillary hair, increased stature, voice deepening, increased bone density/muscle mass, broadening of shoulders, etc.
Oestrogens - uterine growth, endometrial thickening, involved in menstrual cycle, growth of body hair, pelvic widening, strengthens bones, etc.
Define Genotype, Phenotype and Gonadal
GENOTYPIC = refers specifically to an individualʼs sex chromosomes (usually XX or XY)
PHENOTYPIC = determined by an individualʼs internal and external genitalia, expression of secondary sex characteristics, and behaviour
GONADAL = refers specifically to an individualʼs gonads (ovaries or testes)
How does Sex determination occur
After fertilisation, the embryo has a pair of bi-potential gonads (derived from the genital ridge primordia) which can differentiate into male or female gonads.
This is controlled via genetic dependent on whether a developing embryo has XX or XY sex chromosomes:
● XY → Y chromosome contains SRY gene which briefly switches on at week 6-8 of embryonic development, leading to the development of testes
● XX → no SRY gene, so ovaries develop
NB: SRY gene encodes for testes-determining factor
What are the 3 steps of Sexual differentiation
The genital ridge sees 3 types of cell invasion which eventually form the bi-potential gonads:
- Primordial germ cells:
○ Expand from the yolk sac epithelium and migrate to genital ridge
○ Become either oocytes or sperm - Primitive sex cords:
○ Cells of the genital ridge that migrate inwards in columns
○ If no SRY → granulosa cells; cords are poorly defined and cluster around oocytes to form a precursor of the follicle
○ If SRY expressed → Sertoli cells; precursor of the seminiferous tubules form - Mesonephric cells:
○ Originate at lateral edge of genital ridge
○ XX: no SRY influence; vascular tissue + theca cells form
○ XY: pre-Sertoli cells express SRY; vascular tissue, Leydig cells and a basement membrane
Give a brief description of the Primitave sex cords and Mesonepheric cells and function.
Describe the process of Internal genitalia differentiation for both male and female
A gonadal template forms, which then differentiates according to hormonal factors governed by genotypic sex
Female:
● Granulosa cells envelop oocytes, with theca cells mixing in around them
● Mullerian ducts are able to develop due to the absence of the SRY gene (hence, no Sertoli cells and AMH)
● Mullerian ducts: become the upper 3rd of the vagina, uterus and Fallopian tubes
● Wolffian ducts regress because of the absence of testosterone (as there are no Leydig cells present)
Male:
● Sertoli cells secrete AMH causing the Mullerian ducts to regress
● Leydig cells secrete testosterone → stimulate the development
of the Wolffian ducts
● Wolffian ducts: develops into sperm-carrying features of the
male genitalia the seminal vesicles, vas deferens and epididymis
What is the template for external genital differentiation before differentiation occcurs
Genital tubercle → clitoris/glans
Urethral folds → labia minora/penile shaft Genital swelling → labia majora/scrotum Urogenital groove → vaginal opening/perineal raphe
How does differentitation of external genitalia occur
FEMALE:
●Levels of testosterone are insignificant, thus
5-alpha-reductase does not produce much
DHT
● Therefore, female genitalia undergo little change from the original “template”
● Features such as the clitoris and labia remain
MALE:
● Tesosterone levels higher, leading to its conversion to DHT under the stimulatory influence of 5-alpha-reductase
● 5-alpha-reductase binds to androgen receptors causing changes to external anatomy of the “template” genitalia:
a. Clitoris enlarges → penis
b. Labia fuse and form rugae → scrotum
Genital tubercle → clitoris/glans
Urethral folds → labia minora/penile shaft Genital swelling → labia majora/scrotum Urogenital groove → vaginal opening/perineal raphe
How do the testes descent
The testis begins to descend through the posterior abdominal wall via the newly-formed inguinal canal between weeks 25-30. The majority of testes will arrive in the scrotum by week 33. It is an androgen-driven process; below is a simplified version:
● The gubernaculum, a fibrous tissue, guides descent by forming an attachment between the inferior testis and the future scrotum
● Processus vaginalis, an embryonic outpouching of the embryonic peritoneum, precedes the testes and closes (a few weeks before - a few weeks after birth)
What are the different types of sexual differentiation disorder
1. Androgen insensitivity syndrome
○ XY genotype, so individual produces testosterone, but it has little or no effects on targets
○ Caused by defects to the androgen receptor at target cells such as at the i. testes
ii. external genitalia
iii. genital ducts
○ Can be complete or partial
2. Congenital adrenal hyperplasia (CAH)
○ A series of rare, autosomal recessive conditions caused by deficiencies in enzymes involved in steroidogenesis
○ Leads to deranged levels of aldosterone, cortisol or both
3. 5-alpha reductase deficiency
What are the different Androgen Insensitivity Disorder (AIS)
COMPLETE
● Very uncommon (1:20,000)
● Androgen receptors have no function
● SRY still expressed, hence there Mullerian
ducts regress, and so no uterus is present
● Leydig cells make testosterone but Wolffian
ducts are not stimulated
● Therefore, at birth genitals appear female
● DIAGNOSIS: typically occurs at puberty when
patient present with primary amenorrhea + excess serum testosterone (for a patient who thinks they are female)
PARTIAL
● Some androgen receptors do function ● Presentation varies widely, with varying
degrees of penile and scrotal development ● Typically there is a degree of ambiguity with
regards to the morphology of external genitalia
Define Virilization
Virilization is a condition in which a female develops characteristics associated with male hormones (androgens), or when a newborn has characteristics of male hormone exposure at birth
What are the different types of CAH (Congenital Adrenal Hyperplasia) and what is this disorder
1) 21-hydroxylase deficiency
21-hydroxylase deficiency May be complete or incomplete Which is one variation of CAH
Aldosterone and cortisol cannot be produced, causing potentially severe features:
● Hypovolaemia
● Hyponatraemia (=“salt-wasting”)
● Hyperkalaemia
There is also a steroidal shunt towards the production of excess androgens, leading to virilised genitalia
Tx: corticosteroids to correct the HPA axis feedback loop (suppress CRH and ACTH) + treat electrolyte imbalances if present
Tx: means treatment
What are the different types of CAH (Congenital Adrenal Hyperplasia) and what is this disorder
2) 17-alpha hydroxylase deficiency
Cortisol and androgens are unable to be synthesised with this deficiency. Therefore, males present with ambiguous genitalia and females present with primary amenorrhoea.
This leads to a shunt towards excess aldosterone production causing
● Excess tubular Na+ and H2O reabsorption → hypertension (HTN)
● Hypokalaemia
Tx: corticosteroids + antihypertensives
What are the different types of CAH (Congenital Adrenal Hyperplasia) and what is this disorder
3) 1-beta hydroxylase deficiency
Similar to 21-hydroxylase deficiency, but with a more minor shunt towards androgen production, leading to virilisation.
There is a build-up of 11-deoxycorticosterone and 11-deoxycortisol. The latter is not biologically active, but the former is active as a mineralocorticoid.
This leads to increased renal Na+ and H2O reabsorption → hypervolaemia and HTN (+hypokalaemia).
Tx: corticosteroids + antihypertensives
Give an overview of what 5-alpha reductase deficiency is
Individuals with XY chromosomes, will undergo normal changes to internal genitalia (Wolffian ducts grow, Mullerian ducts regress), BUT since 5-alpha reductase is lacking, testosterone cannot be converted to DHT.
Hence, changes to external genitalia that require DHT do not occur.
These patients present with ambiguous or female-appearing genitalia at birth
Confusingly (for individual), excess testosterone at puberty may lead to unexpected virilisation
Define what puberty is
1) Transition from non-reproductive to reproductive state - mature gametes.
2) Profound physiological & psychological changes.
3) Secondary characteristics develop (primary are present at birth).
What is consonance regarding puberty
Consonance; refers to a smooth ordered progression of changes. Regardless how long each pubertal transition takes in any given individual, the order in which the changes happen remains the same.
2 events that start with A and G
What are the endocrine events of puberty
Adrenarche
-maturation of adrenal cells
- release of androgens, leads to pubarche; pubic & axillary hair
Gonadarche
-after adrenarche, HPG axis driven
-synthesis and release of pituitary peptide hormones (FSH, LH), which activate gonadal function
What influences puberty
genes, body fat/nutrition, Kisspeptin
What are the psychological changes during puberty
● Increasing need for independence
● Increasing sexual awareness/interest
● Development of sexual personality
What are the physical changes of Puberty, both female and male
What is tanner staging of puberty developement
Tanner Staging, also known as Sexual Maturity Rating (SMR), is an objective classification system that providers use to document and track the development and sequence of secondary sex characteristics of children during puberty.
There are 5 stages
What is precocious puberty and the central and peripheral characterisitics seen and what causes it
(Early secondary sexual characteristics)
The traditional definition of precocious puberty is the development of secondary sexual characteristics before 8 years of age in girls and 9 years in boys.
An abnormal pituitary gland or hypothalamus may cause precocious puberty. This is referred to as central precocious puberty. Peripheral precocious puberty occurs when sex hormone glands start working earlier than they should.
Central
● Gonadotropin dependent
● Consonance maintained
● Excess GnRH/gonadotropin
secretion
● Accelerated linear growth for
age
● Advanced bone ages
● Increased FSH, LH, E2, T.
● Mx: GnRH analogues, surgery,
radio/chemotherapy
Peripheral
● Gonadotropin independent
● Loss of consonance
● Excess of androgens due to
non-axis related causes eg testotoxicosis, tumors, exogenous steroids, CAH
● Suppressed FSH, LH, increased E, or T.
What is defined as pubertal delay
Absence of secondary sexual maturation by 14 years (boys) or 13 years (girls), or absence of menarche by 18 years.
What is Constitutional delay
Constitutional delay of growth and puberty is a term describing a temporary delay in the skeletal growth and thus height of a child with no physical abnormalities causing the delay. Short stature may be the result of a growth pattern inherited from a parent or occur for no apparent reason.
Affecting both growth and puberty. 90% cases. M>F.
Hereditary in multiple genes, or secondary to chronic illness eg. diabetes, cystic fibrosis.
What are the main reasons for Constitutional Delay
● Hypogonadotropic hypogonadism (low FSH, LH)
● Hypergonadotropic hypogonadism (high FSH, LH)
What is Hypogonadotropic hypogonadism (low FSH, LH) and Hypergonadotropic hypogonadism (high FSH, LH)
Hypergonadotropic hypogonadism results from diseases of the testes while hypogonadotropic hypogonadism from the pituitary or the hypothalamus
hypergonadotropic hypogonadism is a failure of the testes to produce sufficient quantities of testosterone. As part of the feedback response, the pituitary is stimulated to secrete higher levels of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
Male hypogonadotropic hypogonadism (HH) is defined as the failure of the testes to produce androgens and sperm and is a consequence of congenital or acquired diseases that affect the hypothalamus and/or the pituitary gland.
What is Folliculogenesis
Folliculogenesis is the process by which the female germ cell develops within the somatic cells of the ovary and matures into a fertilizable egg
Give an overview of Follicle formation and growth
What are primary and secondary Follicles
Primordial follicle
-primary oocytes packed within cortex of ovary
-ech surrounded by follicular cells (as it grows these become granulosa cells)
-granulosa cells secrete acelluar layer; basal lamina
Secondary follicle
-at puberty, a cohort of follicles initiate growth each day -granulosa cells multiply
-oocytes secrete another layer; zona pellucida
-second vascularized layer of cells surround the basal lamina; theca cells
-follicle widens, increasing space between cells
-this space is filled with follicular fluid; antrum
-these are now secondary (antral) follicles -independent of FSH
oogenesis
Describe the process of Folliculogenesis (Part 1)
● Oogenesis
- Maturation of ova (egg cells)
- Primordial germ cells multiply via mitosis and migrate
to ovaries to become oogonia
- Oogonia undergo further mitosis and enter meiosis I
and become primary oocytes
- All the cells a person will ever have are made at this
stage (pre-birth)
- Oocyte is arrested in cell division prior to second
meiotic division, occurring after fertilization
Follicle Initiation
Describe the process of Folliculogenesis (Part 2)
Follicle initiation; cohort of early follicles grow continuously after leaving pool
- Only continue to grow if they are at correct size to respond to FSH (follicle recruitment)
- One follicle will become dominant and is the only cell to ovulate (dominant follicle selection)
- Occurs during follicular phase of menstrual cycle
2 cell, 2 gonadotropin theory
What are the follicular steroid output
2 cells: granulosa (GCs) and theca cells (TCs)
2 gonadotropins: FSH and LH
○ FSH stimulates the GCs to grow and proliferate
○ The growing GCs produce FSH receptors,
making them responsive to FSH
○ LH stimulates the TCs to produce androgens
and progesterone
○ FSH stimulates the GCs to produce aromatase
enzyme
○ The androgens made by TCs diffuse into the
GCs where they are converted into estradiol
(E2) by aromatase
○ E2 diffuses into circulation
Exception: when a dominant follicle is selected, its GCs acquire LH-receptors, allowing it to control both oestrogen and progesterone production (more of this next week!)
What is contraception
Contraception is the act of preventing pregnancy
Different types of contraception
Fertility awareness;
based on prediction of most fertile period of a cycle
Barrier methods; female diaphragm, male condom
Emergency contraception
- Should be offered ASAP after UPSI (unprotected sexual intercorse)
- Acts by postponing ovulation, so not effective after ovulation
Hormonal methods
-COCP (combined oral contraceptive pills); Inhibition of ovulation by feedback on the HPO axis
-POP (progesterone only pill); Making cervical mucus hostile to sperm Making the endometrium hostile to implantation
Reducing cilia motility in the fallopian tubes
-IUD (Intrauterine device); Kills sperm in 1st part of the cycle; prevents implantation in 2nd part of the cycle*
