Reproduction 2 Flashcards
What is the major hypothalamic hormone in the HPG axis?
GnRH/LHRH- absolutely required and must be released in a pulsatile fashion
What is the major pituitary hormone in the HPG axis?
LH and FSH
What does LH do?
stimulates steroidogenesis in the ovaries and testes
What does FSH do?
stimulates gametogenesis in the ovaries and testes
What are some regulators of GnRH?
Kisspeptin, gonadal steroid hormones
GnIH, prolactin, neurotransmitters (GABA), cortisol (stress), growth factors (TGFα/β), neuropeptides (opiods, melatonin)
Almost all inhibit GnRH
What does Kisspeptin do?
Required to increase release of GnRH at time of puberty.
Presumed signal for pubertal onset
Mutations in KISS1 receptor cause hypogonadotropic hypogonadism
What do inhibins and activins do in the pituitary?
Inhibins inhibit FSH specifically
Activins are expressed in the pituitary and the gonads, stimulate FSH-beta, LH-beta, and GnRH receptor synthesis in the pituitary
Where is inhibin B especially expressed?
gonads
How is LH activated?
via fast GnRH pulses
How is FSH activated?
via slow GnRH pulses
What cells have a high number of FSH receptors?
Sertoli cells: form the blood-testes barrier
What are the six things that FSH stimulates in the testes?
Stimulates spermatogenesis - Increases sperm motility
Stimulates growth of seminiferous tubules – primary determinant of testes size
Stimulates androgen binding protein (ABP) – maintains high local T
Stimulates aromatase
Stimulates inhibin
Stimulates growth factors
What does aromatase do?
Converts estosterone to estradiol
What cells have a high number of LH receptors?
Leydig cells
What effects does LH have on Leydig cells?
Stimulates steroidogenesis from cholesterol
Androgens = 19 carbon steroids
Stimulates StAR protein – rate limiting
Stimulates Leydig cell growth
Where are testosterone precursors made?
extragonadal tissues: brain, adrenal, skin, adipose tissue
What is the primary source of circulating T?
Testes
in what form is testosterone found in the blood?
bound to SHBG
What is testosterone converted to intracellulary
DHT or estrogens
What common receptor does T and DHT bind?
Androgen receptor (AR) - a nuclear steroid receptor
DHT has higher affinity
How much of the daily production of testosterone is excreted as free testosterone?
What is the remaining, non-excreted testosterone converted to?
17-ketosteroids & DHT –> conjugated to water soluble forms and excreted.
What does masculinization of the brain require?
T to E conversion
What is DHT responsible for?
male pattern baldness
during fetal development, what does testosterone stimulate?
epididymis, vas deferens, seminal vesicles
during pubertal development, what does testosterone stimulate?
penis, seminal vesicles, musculature, voice, skeleton, spermatogenesis
during fetal development, what does DHT stimulate?
penis, penile urethra, scrotum, prostate
during pubertal development, what does DHT stimulate?
scrotum, prostate, male pattern hair distribution, beard, sebaceous glands
What is the functional anatomy of the penis?
Glandular and muscular tissue
Penile urethra
What are the male accessory glands?
Seminal vesicles
Prostate gland
Bulbourethral gland (Cowper’s gland)
What is the functional anatomy of the testes?
Seminferous tubules
scrotum
What is cryptorchidism?
“hidden testes”
Most common congenital abnormality of urogenital tract, often result of undescended testes that remain in abdominal cavity
when and where do the testes descend from?
The testes descend from the peritoneal space during embryonic development
Where does counter-current heat exchange happen in the testes?
venous blood in the pampiniform plexus to the blood in the testicular artery
What is the distribution of cell types in the testes?
80% germinal tissue and 20% supportive connective tissue with Leydig cells
What is the peritubular space?
Leydig cells, myoid cells, blood supply
What is the intratubular space?
Sertoli cells, developing germ cells, lumen
Where does spermatogenesis occur?
The adluminal compartment
What creates the blood-testes barrier?
tight junctions between sertoli cells
What is found in the basal compartment?
stem cell niche
What supports sperm development in the lumen?
High T concentrations
What does inhibin do in the testes?
augments LH-induced testosterone production in Leydig cells
What does activin do in the testes?
inhibits LH-induced testosterone production in Leydig cells
What is spermatogenesis?
the process by which spermatogonia become 4 haploid spermatids
What is spermiogenesis?
maturation of spermatids into spermatozoa
What is spermiation?
release of spermatozoa from Sertoli cells into lumen
Where does spermatogenesis, spermiogenesis, and spermiation occur?
all processes occur in the seminiferous tubules
describe the maturation of spermatozoa after release into the lumen
Spermatozoa initially immobile – passive movement from seminiferous tubule to rete testis.
development of the acrosome
Acquisition of receptors necessary for binding to ovum.
Deceased cytoplasm and cell volume.
increased motility
What is the acrosome?
sperm “cap” containing hydrolyzing enzymes used to penetrate ovum
when is sperm maturation fully complete?
when the sperm enters the vagina (capacitation)
What is the composition of semen?
10% sperm (150-600 million)
70% fluid from seminal vesicles
10% fluid from epididymis, prostate, bulbourethral glands
describe the anatomy and function of the seminal vesicles
paired, with inferior bladders, forms the ejaculatory duct
releases fructose, citric acid, other nutrients
pH – seminal vesicle fluid makes semen more alkaline (~7.3-7.7) promotes optimum motility and survival
describe the anatomy and function of the prostate
surrounds prostatic urethra
first fluid to be expelled in ejaculate
secretes factors that prevents clumping of sperm
proteolytic enzymes important for liquefaction of sperm
discuss benign prostatic hyperplasia
PSA used to diagnose prostate growth
describe the anatomy and function of the bulbourethral (Cowper’s) gland
Immediately below prostate
Secretes mucous into urethra upon arousal – pre-ejaculate
What occurs in the flaccid state?
Helicine arteries constrict, restricting blood flow - controlled by tonic sympathetic activity
What occurs in an erection?
relaxation of vascular smooth muscle (corpora cavernosa and corpora spongiosum) leads to increased blood flow in cavernous tissue
Engorgement compresses outflow pathway and creates tumescence (swelling)
What neural control is an erection under?
parasympathetic!
What is the parasympathetic chain of events that leads to an erection?
parasymp neurons release ACh and NO
Ach can bind muscarinic receptors and activate PLC (via Gαq)
This increases calcium and activates NO synthase
NO activates guanylyl cyclase
What do somatic nerves do and what are they important for?
stimulate striated penile muscles causing greater pressure (ischiocavernosus muscle, bulbospongiosus muscle)
important for ejaculatory force, not for maintaining and erection
Discuss the effects of Viagra
Inhibits phosphodiesterases that would normally decrease cGMP
Maintains chronic state of vasodilation
Not specific to penile circulation – can cause heart problems
Still requires CNS arousal
Define emission
movement of the ejaculate into the prostatic/proximal part of the urethra
sets the stage for ejaculation
discuss the sympathetic control of emission
Direct innervation of smooth muscle cells via alpha adrenergic receptors results in peristaltic rhythmic contractions via smooth muscle of portions of vas deferens, seminal vesicles, prostate
What stimulates the ejaculation reflex?
entry of semen to bulbous urethra from prostatic urethra
What is the neural control of ejaculation?
Spinal cord reflex as well as neural control – lack of direct voluntary control
Afferents reach sacral spinal cord (S2-S4) triggering efferent somatic motor neurons via the pudendal nerve
What propels semen through the urethra?
Rhythmic contractions of ischiocavernosus and bulbospongiosus muscles
What are the three categories of male fertility disorders?
Pre-testicular, testicular, post-testicular
What is primary pre-testicular fertility disorder?
hypergonadotropic hypogonadism
High FSH/LH, low T/DHT
ex: Klinefelter syndrome, enzyme deficiencies
What is tertiary/secondary pre-testicular fertility disorder?
hypogonadotropic hypogonadism
Low GnRH, low FSH/LH, low T/DHT
ex: Kallman syndrome, panhypopituitarism, hyperprolactinemia (most common)
What are causes of testicular fertility disorders?
Klinefelters, cryptorchidism
varicocele (dilated scrotal veins - most common cause of subfertility in men) - no counter-current heat exchange
What are causes of post-testicular fertility disorders?
Ductal obstructions, premature ejaculation, impotence
