Male Reproductive Physiology (Lopez) Flashcards
1
Q
How is sex determined biologically?
A
- if Y chromosome present: SRY gene expressed > determines genetic sex (male) > testes develop > determined gonadal sex > Sertoli cells secrete Antimullerian hormone (to prevent development of female characteristics), Leydig cells secrete testosterone > male genital tract and external genitalia (determines phenotypic sex)
- if no Y chromosome present: genetic sex determined by XX chromosomes > ovaries develop > determines gonadal sex > no antimullerian hormone or testosterone produced > female genital tract and external genitalia develop (determines phenotypic sex)
2
Q
How does gonadotropin (LH/FSH) secretion vary over a lifetime?
A
- small amounts secreted as a fetus
- secretion levels off within childhood (FSH > LH)
- levels slowly begin to rise during puberty
- for females, secretion becomes pulsatile during adult reproductive period, which is indicative of the menstrual cycle (LH > FSH)
- for males, secretion remains consistent from puberty to adult reproductive period
- levels slowly begin to rise and remain consistently elevated during senescence (FSH > LH)
3
Q
How is puberty initiated in terms of hormonal signaling?
A
- puberty is initiated by pulsatile secretion of GnRH, which drives pulsatile secretion of FSH and LH
- pulsatile secretion of FSH and LH stimulates secretion of gonadal steroid hormones (testosterone and estradiol)
- increased circulating levels of sex steroid hormones are responsible for appearance of secondary sex characteristics at puberty
- if GnRH analogue is administered in intermittent pulses to replicate nml pulsatile secretion, puberty is initiated and reproductive function is established
- if long-acting GnRH analogue is administered, puberty is not initiated
4
Q
What anatomical structures are involved in male reproduction?
A
- testes
(seminiferous tubules, Sertoli cells, Leydig cells)
- scrotum
- epididymis
- vas deferens
- seminal vesicles
- prostate gland
5
Q
What are the 2 main functions of the testes?
A
- spermatogenesis
- secretion of testosterone
6
Q
What is the main function of the scrotum?
A
keeps testes at a lower temperature than body (1-2° C below) which is essential for spermatogenesis
7
Q
What are the main functions of the epididymis?
A
primary location for maturation and storage of sperm
8
Q
What is the main function of the vas deferens (ductus deferens)?
A
- provides another storage area for sperm (ampulla)
- part of the tract that transports sperm for ejaculation
9
Q
What structures and cell types are within the seminiferous tubules of the testes?
A
- seminiferous tubule: epithelium formed by Sertoli cells, w/ interspersed germ cells
- germ cells: spermatogonia (most immature germ cells, located near periphery of tubule), spermatozoa (mature germ cells, located near lumen of tubule)
- Leydig cells: interstitial cells that lie between tubules
- adult testes: 80% seminiferous tubules and 20% connective tissue interspersed w/ Leydig cells
10
Q
What are the main functions of Sertoli cells?
A
- provide nutrients to differentiating sperm
- form tight junctions w/ each other, creating a barrier between testes and blood stream
- secrete aqeuous fluid into lumen of seminiferous tubule (helps transport sperm through tubules into epididymis)
11
Q
What is the main function of Leydig cells?
A
synthesis/secretion of testosterone
12
Q
What hormones do the testes secrete?
A
- androgens: testosterone, dihydrotestosterone (DHT), androstenedione
- testosterone is most adundant, most of it is eventually converted to DHT
13
Q
What enzymes are necessary for testosterone synthesis in the testes?
A
(major andorgenic hormone, synthesized/secreted by Leydig cells)
- testes lack 21β-hydroxylase and 11β-hydroxylase: no glucocorticoids or mineralocorticoids are synthesized
- testes have 17β-hydroxysteroid dehydrogenase: converts androstenedione to testosterone; end prod of steroid synthesis in testes is T (not DHEA or androstenedione like in adrenal glands)
14
Q
How does testosterone transport and signaling occur?
A
- in lumen of seminiferous tubules, T is concentrated by binding to androgen-binding protein (ABP)
- T diffuses to target cells and binds to androgen receptors (AR)
- T is not active in all androgenic target tissues: in some tissues, DHT is active androgen (e.g. prostate gland in adult and external genitalia in male fetus, skin, liver); 5α-reductase in peripheral tissue converts T to DHT
- most of circulating T is bound to plasma proteins and albumin: sex hormone-binding globulin (SHBG)
15
Q
How is DHT produced and what is the purpose of producing it?
A
- 5α-reductase, in peripheral tissue, converts T to dihydrotestosterone
- DHT also binds to androgen receptors, except w/ greater affinity
- plays important role in causing changes at puberty
- deficiency of 5α-reductase results in ambiguous external genitalia
16
Q
How is estrogen produced in males?
A
- small amnts of estrogen are formed in males
- estrogen conc in seminiferous tubules fluid is quite high: putative source of estrogen is Sertoli cells (product of conversion of T to estradiol mediated by aromatase (CYP19)); potential important role in spermatogenesis (human sperm cells express at least 1 isoform of estrogen receptor)
- larger amnts of estrogens are prod from T and androstenediol in other tissues of body (esp adipose tissue): accounts for as much as 80% of total male estrogen prod
17
Q
What is the rate limiting step of testosterone production (and androgen prod in general)?
A
- conversion of cholesterol to pregnenolone
- mitochondrial pathway for T synthesis: cytochrome P450 side-chain cleavage (P450SCC) enzyme removes side-chain (carbons 22-27) from carbon at position 20 of cholesterol > pregnenolone
18
Q
How is testosterone synthesized/secreted from Leydig cells?
A
- cholesterol > (P450SCC) > pregnenolone > (3β-HSD) > progesterone > (17-hydroxylase) > 17(OH)-progesterone > androstenedione > (type III 17β-HSD) > testosterone
- Leydig cells make limited amnts of DHT and estradiol-17β
- T diffuses into seminiferous tubules and peritubular capillary network to be carried into peripheral circulation: in seminiferous tubules, T is conc by binding to ABP; T is carried to peripheral circulation by SHBG and albumin
19
Q
How do Leydig cells acquire/store cholesterol?
A
- Leydig cells 1) synthesize cholesterol de novo; they can also 2) acquire it from circulation through LDL and HDL receptors
- store cholesterol as cholesterol esters
- free cholesterol is generated within the testis, particularly in Leydig cells, by cholesterol hormone-sensitive lipase (HSL): converts cholesterol esters to free cholesterol for androgen production
- cholesterol is then transferred within mitochondrial membranes via steroidogenic acute regulatory protein (StAR) and then converted to pregnenolone
20
Q
What is the role of LH in testosterone production?
A
- LH stimulates conversion of cholesterol to pregnenolone and regulates overall rate of testosterone synthesis by Leydig cells
- LH promotes pregnenolone synthesis in 2 ways: increases affinity of P450scc enzyme for cholesterol; stimulates synthesis of P450scc enzyme (long-term action)
(*another name for P450scc is cholesterol desmolase)
21
Q
What are the possible fates of testosterone?
A
- as T enters peripheral circ, it quickly reaches equilibrium w/ serum proteins: ~60% of circ T is bound to sex hormone-binding globulin (SHBG), ~38% of circ T is bound to albumin, ~2% remains as free T which is the most biologically important form
- T and its metabolites are excreted primarily in urine: ~50% of excreted androgens are found as urinary 17-ketosteroids; remainder being conjugated androgens or diol/triol derivatives
22
Q
What are the actions of testosterone on fetal development?
A
- T is present at 2nd month of embryonic life, presence/absence of T determines development of genital organs/characteristics: (+) T > penis, scrotum; (-) T > clitoris, vagina
- fetal actions: differentiation of internal male genital tract (epididymis, vas deferens, seminal vesicles); causes descent of testes into scrotum during last 2-3 months of pregnancy (cryptorchidism: lack of decent)
26
Q
What are the anabolic actions of androgens within male development?
A
- stimulate erythropoietin synthesis (red blood cell prod)
- stimulate sebaceous gland secretion
- control protein anabolic effects (nitrogen retention)
- stimulate linear body growth, bone growth, and closure of epiphyses
- stimulate ABP synthesis
- maintain secretions of sex glands
- regulate behavioral effects (e.g. libido)
28
Q
What is the intracellular mechanism of action of testosterone?
A
- Leydig cells, LH receptor (cAMP-PKA pathway): results in steroidogenesis and testosterone prod; testosterone diffuses into seminiferous tubules and peripheral circulation
- Sertoli cells stim by T and FSH (cAMP-PKA pathway): results in protein synthesis and prod of inhibin (inhibits FSH release), ABP, aromatase, and other products
29
Q
What is the role of testosterone in Sertoli cells?
A
- FSH stimulates Sertoli cells to secrete ABP into lumen of seminiferous tubules
- binding of T in lumen provides a local T supply for developing spermatogonia
- aromatiziation of T to estradiol-17β also occurs within Sertoli cells
32
Q
What are the endocrine functions of Sertoli cells?
A
- expression of ABP, T, and FSH receptors
- prod of Antimullerian hormone (AMH)
- aromatization of T to estradiol-17β
- prod of inhibin to regulate FSH levels
33
Q
What are the 3 phases of spermatogenesis?
A
1) mitotic divisions
2) meiotic divisions
3) spermiogenesis
35
Q
Describe the 2nd phase (meiotic divisions) of spermatogenesis:
A
(production of haploid gamete)
- primary spermatocytes undergo 2 meiotic divisions
- first division produces 2 secondary spermatocytes, each w/ a haploid number of duplicated chromosomes
- secondary spermatocytes enter second meiotic divison, producing 2 spermatids, each w/ a haploid number of unduplicated chromosomes
36
Q
Describe the 3rd phase (spermiogenesis) of spermatogenesis:
A
(maturation)
- spermatids undergo spermiogenesis and mature into spermatozoa
- nuclear and cytoplasmic changes produce mature spermatozoa
- ends in testis w/ release of spermatozoa from Sertoli cells
37
Q
What structural changes occur within spermatozoon during spermiogenesis?
A
39
Q
What happens when exogenous testosterone is administered?
A
- increased circulating androgen levels exert negative feedback of anterior pituitary to lower LH secretion below normal
- lowered LH levels leads to lower endogenous T production by Leydig cells, which leads to lowered intratesticular levels of T
- lower intratesticular levels of T leads to insufficient spermatogenesis
40
Q
How do the plasma testosterone and sperm production levels vary throughout the stages of male sex function (fetal, neonatal, pubertal, adult, old age)?
A
42
Q
What is the function of seminal vesicles?
A
- secrete mucoid material containing nutrients, prostaglandins, and fibrinogen
- adds considerable nutrient value for ejaculated sperm
- prostaglandins aid in fertilization: react w/ female cervical mucus to make it more receptive to sperm movement (make cervical mucus less thick); cause backward, reverse peristaltic contractions in the uterus and fallopian tubes to move ejaculated sperm toward ovaries
43
Q
What are the functions of the prostate gland?
A
- secretes a thin, milky fluid containing Ca2+, citrate ion, phosphate ion, clotting enzyme, and profibrinolysin (secreted during emission)
- helps w/ pH adjustment: slightly alkaline prostatic fluid helps neutralize acidity of other seminal fluids during ejaculation and thus enhances motility/fertility of sperm
45
Q
How are sperm conveyed within the reproductive tract?
A
- once spermatozoa emerge from efferent ductules, they leave gonad and enter extratesticular portion of reproductive tract (epididymis, vas deferens, ejaculatory duct, prostatic urethra, membranous urethra, penile urethra)
- two main differences from female tract: continuous lumen from seminiferous tubule to end of male tract (i.e. the tip of penile urethra); male tract connects to the distal urinary tract (i.e. male urethra)
46
Q
Describe the process of erection in men:
A
- neurovascular event
- 3 erectile bodies in penis: 2 corpora cavernosa and 1 corupus spongiosum (composed of anastomosing network of potential cavernous vascular spaces lined w/ continuous endothelia within loose CT support)
- during flaccid state: blood flow to erectile tissue is minimal due to vasoconstriction of vasculature
- during erection: parasympathetic nerves innervating vascular SM of helicine arteries that supply blood to cavernous spaces release NO
- NO activiates guanalyl cyclase: increases cGMP, decreases intracellular Ca2+, causes relaxation of vascular SM
- vasodilation allows blood to flow into spaces, causing engorgement and erection
- engorged tissue presses veins against noncompliant outer fascia, reducing venous drainage
- somatic stimulation increases contraction of muscles at base of penis, further promoting erection
47
Q
Describe the process of emission in males:
A
- movement of semen from epididymis, vas deferens, seminal vesicles, and prostate to ejaculatory ducts
- under sympathetic control (adrenergic transmitter)
- causes sequential peristaltic contraction of SM of vas deferens, closing internal sphincter of bladder: prevents retrograde ejaculation of semen into bladder (destruction of sphincter by prostatectomy often results in retrograde ejaculation)
- emission normally precedes ejaculation but also continues during ejaculation
48
Q
Describe the process of ejaculation in males:
A
- propulsion of semen out of the male urethra
- caused by rhythmic contraction of bulbospongiosus and ischiocavernous muscles (striated muscles), which surround the base of the penis
- striated muscles are innervated by somatic motor nerves, contraction causes semen to exit rapidly and outwardly through urethra
51
Q
- genetic disorder that occurs when GnRH neurons fail to migrate into hypothalamus during embryonic development
- sx: delayed/absent puberty and impaired sense of smell
- form of hypogonadotropic hypogonadism
- occurs more often in males
A
Kallman’s syndrome
52
Q
- genetic condition where individuals have 47,XXY genotype
- individuals are phenotypically male b/c of the presence of Y chromosome, thus they appear male at birth
- at puberty, increased levels of gonadotropins fail to induce normal testicular growth/spermatogenesis
- androgen prod is usually low (highly variable among individuals), whereas levels of gonadotropins are elevated (indicating primary hypogonadism)
- seminiferous tubules are largely destroyed, resulting in infertility
A
Klinefelter’s syndrome
(seminiferous tubular dysgenesis)
53
Q
How does prolactin secretion affect FSH/LH secretion?
A
prolactin suppresses FSH and LH secretion
