Male Reproductive Physiology Flashcards
what is the difference between sex and gender?
Sex: refers to a persons biological status (male female or intersex)
-indicators include: sex chromosomes, gonads, internal reproductive organs, and external genitalia
Gender: refers to the attitudes, feelings, and behaviors that a given culture associates with a persons biological sex
what is gender identity, gender expression, and sexual orientation?
gender identitiy: refers to ones sense of oneself as male or female or transgender
Gender expression: way in which a person acts to communicate gender within a given culture, may or may not be consistent with socially prescribed gender roles
Sexual orientation: refers to the sex of those to whom one is sexually and romantically attracted
what is the genetic, gonadal, and phenotypic sex differentiation and when does it begin to develop
Genetic sex: determined by the sex chromosomes, Xy or XX
- During the first 5 weeks of gestational life, the gonads are bipotential (neither male or female)
- Gestational weeks 6-7 the testes begin to develop in genetic males
- Gestational week 9 the ovaries begin to develop in genetic females
Gonadal sex: testes or ovaries
Phenotypical sex: Physical characteristics of the internal tract and the external genitalia
-determined by hormonesH
How does gonadotropin secrertion fluctuate through life
Increased in the fetus then will plateu in childhood
then increase during puberty
during adult reproductive period for females, it will pulsate and males will stay constant
in Senescence, gonadotropin will greatly increase for females and increase for males
how does GnRH play a role in puberty? what happens if GnRh analogue is administered in pulses? what happens if long-acting GnRH is administered?
Puberty is initiated by the pulsatile secretion of GnRH which drives the pulsatile secretion of FSH and LH
-FSH and LH stimulate secretion of gonadal steroid hormones, testosterone ad estradiol
If GnRH analogue is administered in intermittent pulses to replace the normal pulsatile secretion puberty is initiated and reproductive function is established
if Long acting GnRH analogue is administered puberty is not initiated
Function of the Testes, Scrotum, and Epididymis
Testes: two main functions are spermatogenesis and secretion of testosterone
Scrotum: its lower temperature is essential for spermatogenesis (1-2 degrees C below the body temperature)
Epididymis: primary location for the maturation and storage of sperm
Function of the Vas Deferens, Seminal vesicles, and prostate gland?
Vas Deferens: the route the sperm travels to exit into the urethra, also provides another storage area for sperm (ampulla)
Seminal vesicle: secretes fluid rich on citrate, fructose, prostaglandins, and fibrogen
Prostate gland: secrete milky aqueous solution that is rich in citrate, calcuim and enzymes
what is the seminiferous tubule made from, and what are 3 different cells found around it?
Seminiferous tubule is epithelium formed by the sertoli cells, with intersperssed germ cells
- Spermatogonia: most immature germ cells located near the periphery of the tubule
- Spermatozoa: mature germ cells, located near the lumen of the tubule
also interstitial cells that lie between the tubules are the Leydig cells
What are the general functions of the sertoli and leydig cells?
Sertoli:
- provide nutrients to the differentiating sperm
- form tight junctions with each other to create a barrer between the blood and the testes
- secrete an aqueous fluid into the lumen of the seminiferous tubule that helps transport sperm into the epididymis
Leydig cell:
-synthesize and secrete testosterone
what male sex hormones does the testes secrete? what is the most abundant? what are they converted too?
Androgens secreted by the testes include:
- testosterone
- dihydrotestosterone
- androstenedione
Testosterone is the most abundant and is the major androgenic hormone
In target tissues, much of the testosterone is eventually converted to dihydrotestosterone (DHT)
what enzymes do the testes lack, and what enzyme do they contain and what is its function?
The testes lack 21B-hydroxylase and 11B-hydroxylase therefore no glucocorticoids or mineralocorticoids are synthesized here unlike the adrenal gland
The testes have 17B hydroxysteriod dehydrogenase that converts androstenedione to testosterone
-therefore the end product of steroid synthesis in the testes is testosterone and not DHEA and androstenedione
What happens to testosterone in the lumen of the seminiferous tubule?
Testosterone is concentrated by binding to androgen-binding protein (ABP)
since in some tissues Testosterone is not the most active form, what is and how is it converted to it?
in some tissues Dihydrotestosterone is the actice androgen (DHT)
5a-reductase in the peripheral tissue converts testosterone into duhydrotestosterone
what does testosterone bind too when circulation in the plasma?
Albumin or sex hormone binding globulin (SHBG)
What are the functions of the Leydig cells? and how does it work with cholesterol?
Synthesize cholesterol de Novo
-can also aquire cholesterol from LDL and HDL
Store cholesterol as cholesterol esters
-free cholesterol is generated in testis by a hormone sensitive lipase (HSL) converting the cholesterol esters to free cholesterol to then be used to produce androgens
Cholesterol is then transfered within the mitochondiral membranes via steroidogenic acute regulatory protein (StAR) to where it is converted to pregnenolone to begin the process of androgen formation
the Leydig cells also make a limited amount of DHT and estradiol 17B
Production of estrogen in the male? and its effects on spermatogenesis?
Small amounts of estrogens are formed in the male
in the fluid of the seminiferous tubules the estrogen concentration is quite high
Putative source of estrogen is the Sertoli cells
-product of the conversion of testosterone to estradiol is mediated by aromatase
Potential important role in spermatogenesis
-human sperm cells express at least one isoform of the estrogen receptor
Much larger amounts of estrogens are formed from testosterone and androstendiol in other tissues of the body especially the liver
Biosynthetic pathway of androgens and what is the rate limiting step?
Pregnenolone to 17A Hydroxypregnenolone
-17a hydroxylase
17a Hydroxypregnenolone to DHEA
-17,20 Desmolase
DHEA to Androstenediol
-17B Hydroxysteroid dehydrogenase
Andriostenediol to Testosterone
-3B-hydroxysteroid dehydrogenase
Rate limiting step is the conversion of cholesterol to pregnenolone
-need the cytochrome P450 side chain clevage in the mitochondrial pathway to remove the sidechains off the carbon 20 position of cholesterol
How does LH affect the process of testosterone production?
Lutenizing Hormone (LH) stimulates the conversion of cholesterol to pregnenolone and regulates the overall rate of testeosterone synthesis by the leydig cell
LH promotes pregnenolone synthesis in two ways:
- increases the affinity of P450scc enzyme for cholesterol
- stimulates synthesis of P450scc enzyme (long term action)
another name of P450scc is cholesterol desmolase
when does testosterone production begin? and what does Androgen bind to once made?
begins at 7-8 weeks gestiation
Androgens diffuse to target cells and bind androgen receptors (AR)
- found in prostate, testis, epididymis, seminal vesicles
- CNS, anterior pituitary, thyroid, adrenal cortex, liver, kidney tubules, bladder, cardiac and striated muscle, bone
- in female, ovary, mammary glands, uterus
AR is a nuclear receptor which directs protein synthesis
what happens if their is a deficiency in DHT production?
Deficiency in 5a-reductase results in ambiguous external genitalia
DHT is important in causing changes at puberty
what are the fates of testosterone?
60% of circulating Testosterone is bound to sex hormone binding globulin
38% of circulating Testosterone binds to albumin
2% remains as Free testosterone which is most important biological form
Testosterone and its metabolites are secreted primarily in the urine
- 50% excreted androgens found as urinary 17-ketosteroids
- remainder being conugated androgens or diol or triol derivatives
What are testosterones actions during fetal development?
Present as 2nd month of embryonic life
Presence or absence determies development of genital organs and characteristics
- +testosterone = penis, scrotum
- no testosterone = clitoris, vagina
Fetal differentiation of the internal male genitalia tract (epididymis, vas deferens, and semina; vesicles)
Causes descent of testes into the scrotum during last 2-3 months of pregnancy
what is Cryptorchidism?
lack of testes descent
What are testosterones actions at pubery?
- Increased muscle mass
- pubertal growth spurt
- closure of the epiphyseal plates
- growth of the penis and seminal vesicles
- deepening of the voice
- spermatogenesis
- libido
what are the specific actions of DHT?
Fetal differentiation of the external male genitalia (penis, scrotum, and prostate)
Male hair distribution and male pattern baldness
Sebaceous gland activity
Growth of the prostate
What can 5a reductase inhibitors be used for
Treatment for benign prostatic hypertrophy
What are androgenic actions?
Regulation of differentiation of male internal and external genitalia
timulation of growth, development of secondary sexual characteristics at puberty
Maintenance of reproductive tract and production of semen
Initiation and maintaince of spermatogenesis
What are some anabolic actions of Androgens
Stimulation of erythropotein synthesis (stimulates red blood cell production)
stimulation of sebaceous gland secretion
control of protein anabolic effects (nitrogen retention)
Stimulation of linear body growth, bone growth and closure of epiphyses
stimulation of ABP synthesis
Maintenacne of secretions of sex glands
regulation of behavioral effects including lipido
What is benign prostatic hyperplasia
By age 80 over 80% of men will have BPH
Symptoms: urinary frequency, urinary urgency, nocturia, difficulty initiating and maintaining a urinary stream, a feeling of postvoid fullness in the bladder and dribbling
Concentrations of DHT in prostatic tissue are not higher in men with BPH then those who dont
BPH paitents might have more DHT receptors on their prostates
What are the intracellular mechanisms of LH and FSH?
LH on leydig cell
- cAMP-PKA pathway to increase protein synthesis
- leads to steroidogenesis and testosterone production
- testosterone diffuses into seminiferous tubules and peripheral circulation
Sertoli cell stimulated by FSH and testosterone
- cAMP-PKA pathway to increase protein synthesis
- results in protein synthesis and production of inhibin (inhibits FSH reslease), ABP aromatase and other products
How are sertoli cells stimulated and what are their supportive, exocrine, and endocrine functions?
FSH stimulates sertoli cells to secrete ABP into the lumen of the seminiferous tubules
Binding of testosterone in the lumen also provides local testosterone supply for the developing spermatogonia
Supporitive function:
- Maintaining blood testis barrier
- Phagocytosis
- Transfer of nutrients from blood to sperm (transferrin, Fe, lactate)
- Receptors for hormones and paracrines
Exocrine function:
- Production of fluid
- Production of ABP
- Determination of release of sperm from seminiferous tubule
Endocrine function:
- Expression of ABP, T, and FSH receptors
- production of ANtimullerian hormone (AMH)
- Aromatization of T to estradiol-17B
- Production of inhibin to regulate FSH levels
Hypothalamic-Pituitary gonadal axis
GnRH released from hypothalamus
acts on anterior pituitary to release LH and FSH
FSH acts on sertoli cells
- ABP
- Estrogens
- Spermatogenesis
LH acts on Leydig cell to make androgens
Negative feedback:
- androgens negative feedabk on anterior pituitary and hypothalamus
- inhibin from setoli cells negative feedback on anterior pituitary to stop FSH
where does spermatogenesis occur and how long does the process take?
Occurs along the seminiferous tubules
THe seminiferous tubules are lined by complex stratified epithelim containing two distinct populations of cells, spermatogenic cells that develop into spermatozoa and sertoli cells which have a supportive and nutrient function
the whole process takes 64 days
-process is staggered to allow a group of cells to enter maturation every 16 days
what are the three phases of Spermatogenesis
1) mitotic divisons
- Proliferative phase
- at puberty mitotic cycles increase and spermatoogonia or stem cells divide to produce daughter spermatogonia
- after the last division the resulting cells are called primary spermatocytes
2) Meiotic divisions
- Primary spermatocytes undergo two meiotic divisions
- the first divison produces two secondary spermatocytes each with a hapoid number of duplicated chromosomes
- secondary spermatocytes enter second meiotic divison producing two spermatids, each with a haploid number of unduplicated chromosomes
3) spermiogenesis
- Spermatids undergo spermiogenesis and mature into spermatozoa
- nuclear and cytoplasmic changes to produce mature spermatozoa
- ends in testis with release of spermatozoa from sertoli cells
what happens to the residual body of the spermatozoan?
phagocyttized by sertoli cells
what are the three hormones that stimulate spermatogenesis?
Luteinizing hormone: LH
- secreted by anterior pituitary
- stimulates the leydig cells to secrete testosterone
Follicle stimulating hormone (FSH)
- secreted by anterior pituitary
- stimulates the sertoli cells to nurse and from sperm
Growth hormone:
- Necessary for controlling background metabolic functions of the testes
- promotes early division of the sperm themselves
- without it, as seen in pituitary dwarfs, spermatogenesis is severely deficient or absent
Testosterone:
-essential for growth by division of the testicular germinal cells, which is beginning of sperm formation
Estrogens:
- formed from the testosterone by the sertoli cells when they are stimulated by FSH
- might be essential for spermatogenesis
how does administration of exogenous testosterone affect the regulation of spermatogenesis
it increases the negative feedback loop inhibiting the pituitary and hypothalamus
therefore there is lower amounts of intratesticular levels of T and no insufficient spermatogenesis
what occurs in the Epididymis?
Sperm maturation
Sperm spend an average of a moth in the epidydimis undergoing furthur maturation after release from the testis
Sperm are weakly mobile upon entering the epididymis but strongly motile upon exiting
Decapacitation occurs here, which involves adding molecules to the membranes of sperm to prevent the acrosomal reaction before contact with an egg
can act as storage site for mature sperm for several months
what is the function of the seminal vesicle?
Secretes a mucoid material containing fructose, citric acid, and other nutrient substances as well as prostaglandins and fibrinogen
Adds considerable nutrient value for ejaculated sperm
Prostaglandins aid in fertilization
- react with the female cervical mucus to make it more receptive to sperm movement
- cause backward, reverse peristalic contractions in the uterus and fallopian tubes to move the ejaculated sperm toward the ovaries
Functions of the prostate gland?
Secretes a thin, milky fluid that contains Ca+, citrate ion, phosphate ion, a clotting enzyme and a profibrinolysin
-secreted during emission
pH adjustment:
-the slightly alkaline prostatic fluid helps neutralize the acidity of the other seminal fluids during ejaculation thus enhances the motility and fertility of the sperm
What is semen? and how long can semen live once ejaculated?
Composed of fluid and sperm from the vas deference, fluid from the seminal vesicles, fluid from the prostate, and small amounts of from the bulbourethral gland
Final pH = 7.5
-alkaline fluid neutralizes the mild acidity of the other semen components
Sperm can live for many weeks in the male genital tract
once the sperm cells are ejaculated in the semen their maximal life span is 24-48 hours at body temperature
Each ejaculation contains 2-6ml, 200 million sperm, lower then 20 million = infertile
what are two main differences between the male reproductive tract and the female
The males is continuous lumen from the seminiferous tubule to the end of the male tract (tip of the penile urethra)
The male tract connects to the distal urinary tract
The Erection and what are the 3 erectile bodies in the penis? and what is the physiology behind it?
Neurovascular event
3 erectile bodies in the penis: 2 corpora cavernosa and 1 corpus spongiosum
-Composed of an anastomosing network of potential cavernous vascular spaces lined with continuous endothelia within a loose connective tissue support
During the flaccid state blood flow to the erectile tissue is minimal due to vasoconstriction of vasculature
During erection: parasympathetic nerves innervating the vascular sm of the helicine arteries that supply the cavernous spaces releases NO
- NO activates guanylyl cyclase increasing cGMP and decreases intracellular Ca and causes relaxation of the vascular sm
- Vasodilation allows blood to flow into the smaces causing engorgement and erection
- the engorged tissue presses the veins against a non compliant outer fascia, reducing venous drainage
- somatic stimulation increases contraction of muscles at the base of the penis further promoting erection
THe male sexual response: Emission
In the movement of semen from the epididymis, vas deferns, seminal vesicles and prostate to the ejaculator ducts
-process is under sympathetic control (adrenergic transmitter)
Causes sequential peristaltic contraction of SM of vas deferens closing the internal sphincter of the bladder
- prevents retrograde ejaculation of the semen into the bladder
- emission normally precedes ejaculation but also continues during ejaculation
The male sexual response: Ejaculation
The propulsion of semen out of the male urethra
Caused by the rhythmic contraction of the bulbospongious and the ischiocavernous muscles which surround the base of the penis
- these striated muscles are innervated by somatic motor nerves
- contraction causes the semen to exit rapidly and outwardly through the urethra
Capacitation of the spermatozoa
Sperm are mature when they leave the epididymis but their activity is held in check by secretions from the genital duct epithelial
The changes that occur when they come in contact with the fluids of the female tract allow for capacitation of the sperm
- uterine and fallopian tubes wash away inhibitory factors
- loss of cholesterol that had built up on the acrosome
- membrane of the sperm is much more permeable to Ca+ this increasing the motillity of the sperm
Sperm Acrosome reaction
Large quantities of hyalurinidase and proteolytic enzymes are stored in the acrosomal head of the sperm
- hyaluronidase depolymerizes hyaluronic acid polymers in the intercellular cement that hold the ovarian granulosa cells together
- proteolytic enzymes digest proteins in the structural elements of tissue cells that adhere to the ovum
Testosterone deficiency effects depend upon the age of onset: 2nd-3rd month of gestation? 3rd trimester of pregnancy? Puberty? Post-puberty?
2nd-3rd months of gestation: results in varying degrees of ambiguity in the male genitalia
-Male pseudohermaphrodism
3rd trimester of pregnancy: leads to problems with testicular descent along with a micro penis
-cryptorchidism
Puberty: leads to poor secondary sexual development and overall eunuchoid features
-enuchoidism: persistence of prepubertal characteristics and often by the presence of characteristics typical of the opposite sex
Post puberty: leads to decreased libido, erectile dysfunction, decrease in facial and body hair growth, low energy, and infertile
Kallmans syndrome
Genetic disorder that occurs when FnRH neurons fail to migrate into the hypothalamus during embryonic development
- delayed or absent puberty and an impaired sense of smell
- forms hypogonadotropic hypogonadism
Klinefelters syndrome
Klinefelter syndrome: male with an extra X chromosome
- phenotypically male and apperance of male at birth
- puberty, increaed levels of gonadotropins fail to induce normal testicular growth and spermatogenesis
- androgen production is low where as the levels of gonadotropin are elevated therby indicating primary hypogonadism
- seminiferous tubules are largely destroyed, resulting in infertility
Classification of Primary hypogonadism
decrease Testosterone and increase in LH
i.e. klinefelters syndrome
Classification of secondary hypogonadism
decrease in Testosterone, decrease or normal LH
pituitary dysfunction decrese LH and FSH
Hypothalamic dysfunction: kallmanns syndrome: decrease in GnRH
differnece between tumors of testis and germinal epithelial tumors
Tumors of testis (intersitital cell tumors) produce large amounts of testosterone
Germinal epithelial tumors produce no hormones
Andropause?
as men age, gonadal sensitivity to LH decreases and androgen production drops
LH and FSH levels rise
testosterone decreases slowly after 40
-decreaased bone formation, musle mass, growth of facial hair, appetite, libido
sperm production begins to decline after 50
loss of sexual activity typically about 68-70 years of ace
