Flashcards in Male reporoductive physiology Deck (82):
What are the components of the system and their general function?
Vas-sperm carrier, seminal vesicle- semen secretion, prostate- acid phosphatase, protease, and PSA; Epididymis-sperm storage and maturation; Testis- sperm and steroid hormones
How does sex differentiation occur in the male?
establish chromosomal and gentic sex in zygote, determination of gonadal sex by genetic (Y chromosome with SRY, AMH, Y needed for spermatogenesis), set up of leydig cells in testis first and regression of mullerian duct, then external genitalia forms then UG sinus with prostate all way earlier then female sexual development would occur (ends by about 60 days, earliest female sex differentiation between 60-70 days)
How do we know it the SRY that determines sex?
XXmales and XY females with aberrant Y to X interchange during paternal spermatogenesis, Y specific loci on X
What is the DSS locus in Xp21 region associated with?
46 XY individual leads to testicular dysgenesis and male-to-female sex reversal, deletion does not affect normal testis formation, duplication in 46xx does not affect ovary formation
What does DAX1 overlap with? What is it essential for in the embryo? What suppresses it?
DSS-locus; suppresses SF-1 gene; essential for normal development of adrenal and pituitary glands during embryonic life; suppressed by SRY
What are deletions and mutations in DAX1 associated with?
adrenal hyperplasia and hypogonadal hypogonadism
What does the SF-1 gene do?
essential for activating SOX9 gene which leads to sertoli formation, also stimulate AMH production by sertoli cells and expression of steroidogenic enzymes in Leydig cells,
What does WT1 gene do?
wilm's tumor suppressor gene, involved in early gonadal development, heterozygous deletion results in wilms tumor and gonadal dysgenesis in both sexes as well as ambiguous genetalia in males
What is the result of a mutation in one allele in SOX9 gene?
Campomelic dysplasia, skeletal malfunction syndrome and gonadal dysgenesis in 46XY individuals
What does SRY mediate in testes differentiation?
sertoli cell differentiation and incorporation of germ cells in primitive seminiferous cord; germ cell proliferation is suppressed and differentiation is arrested at primitive spermatogonial stage
What do the sertoli cells do during testes differentiation?
secrete AMH that causes dissolution of mullerian ducts by apoptosis, secrete inhibin, stem cell factor, androgen binding protein, nurture germ cells and prevent meiosis
What do the leydig cells do during testes differentiation?
start testosterone biosynthesis by 9th wk in response to hCG
What does testosterone do during testes differentiation?
stimulates development of male external genitalia and UG sinus; hormonal differentiation continues until puberty is completed and reproductive ability achieved
What causes the sex differentiation in male and female brains?
unclear if testosterone or estrogen causes this
When are morphological sex differences in the brain apparent?
When is gender identity established?
18-20 months; development of secondary sex characteristics opposite does not change this
What is typical kinefelter syndrome?
47XXY karyotype, seminiferous tubule dysgenesis, atrophic testis with hyalinization of ST, impaired sertoli function-> decrease inhibin B, primary hypogonadism and infertility, gynecomastia, prepubertal basal [FSH and LH] within normal but are elevated in postpubertal, low plasma T, higher E2:A, leydig aggregation (hypertrophy but low number), differentiation of testis and lack of ovarian differentiation, congenital anomalies, abnormalities in thyroid function, higher risk of osteoporosis, chronis pulmonary disease and varicose veins with stasis ulcers
What causes the abnormal karyotype in typical klinefelters?
nondisjunction of sex chromosomes during 1st or 2nd meiotic division of germ cells of either parent, can occur at mitotic non-disjunction in zygote after fertilization-> 46 XY can yield 47XXY and 45Y cell line dies
What causes hyalinization in testes in Klinefelter's?
high levels of gondadotropins; 48XXXY boys exhibit precocious puberty and extensive hyalinization 47XXY with gonadotropin deficiency do not have hyalinization
With the gynecomastia in klinefelters what are they at an increased risk of?
predisposition of breast cancer
What causes low testosterone and high estrogen in Klinefelter's?
LH overstimulate leydig cells aromatase activity resulting in conversion of testosterone to E2-17B (subnormal for females)
What congenital anomalies occur with Klinefelter's?
taller than chronological age bcuz disproportionate leg length, lower verbal IQ, poor motor control and delayed emotional development most boys need help in reading and spelling
What thyroid function abnormalities occur in Klinefelters?
diminished response to TSH and decrease iodide uptake
What is 46XY/47XXY mosaicism?
second most common karyotype in Klinefelters, presence of normal cell line modifies clinical expression on 47XXY cell line; secondary sex charcteristics more normal, phenotype less severe, soermatogenesis more common, some are fertile
What is 48XXYY?
typical Klinefelter's with additional features- delinquent behavior, MR and stasis demratitis
What are the characteristics of 46XX male? Causes?
male phenotype and psychosocial orientation but similar clinical and endocrinological defects of Klinefelter's ; loss of Y in embryogenesis, translocation of testis determing gene on an x chromosome or autosome, cryptic sex chromosome mosaicism with undetected cell line with Y chromosome or mutation involving n autosomal or X-linked gene in the pthway to testis differentiation
When does puberty in males begin? End?
When and what occurs with Pubarche and adrenarche?
1-2 yrs before gonadal function, adrenal glands start secreting androgen; 1-1.5 years after genital stage pubic hair starts to appear; sebaceaous secretion occurs and acne formation; set up of HPT axis, GnRH frequency increase necessary for LH
During prepuberty what keeps GnRH suppressed?
GABAnergic neurons in hypothalamus stimulated by 5aDHT which it converts from testosterone; GABA inhibits GnRH secretion from hypothalamus
In the adult What inhibits and what stimulates GnRH release?
Opiodergis neurons inhibit; Adrenergic neurons increase amplitude and frequency of GnRH
How are the Opiodergic neurons regulated during adulthood? What is the affect to GnRH?
T conversion to 5aDHT stimulates opiodergic decreasing GnRH pulse frequency
How are the Adrenergic neurons regulated during adulthood? What is the affect to GnRH?
Testosterone conversion to E2 in the hypothalamus suppresses adrenergic neurons-> decreased amplitude and frequency of GnRH secretion
What male hormones feedback on FSH ?
T conversion to E2 by hypothalamus suppresses FSH secretion in pituitary
What changes in the regulation of GnRH at puberty?
maturity of opiodergic neurons and adrenergic neurons to increase set point of negative feedback; activates GnRH neurons in Preoptic and Arcuate nuclei, onset associated with LH surge, FSH levels rise first followed by LH surge
What occurs in the 2nd genital tanner stage for males?
enlargement of scrotum and testis, change in scrotal skin texture, slight increase in pigmentation; 11.5-12.5
What occurs in the 3rd genital tanner stage for males?
penile growth-length and breadth, testis growth; 12.5-13.5
What occurs in the 4th genital tanner stage for males?
further penile growth and development of glans, growth of testis and enlargement of scrotum; 13.5-15; continued penis growth till 17
What occurs in the 2nd pubic hair tanner stage for males?
sparse long slightly pigmented downy hair at base of penis; 12-13
What occurs in the 3rd pubic hair anner stage for males?
darker coarse hair at the pubes junction; 13-14
What occurs in the 4th pubic hair tanner stage for males?
adult type hair but in smaller area; 14-15
What occurs in the 5th pubic hair tanner stage for males?
adult type quantity and spreading to medial surface of thighs; 15-16
What causes the increase in testicular volume during puberty?
growth of seminiferous tubules, enlargement of leydig cells and testosterone secretion; nocturnal emission mid-puberty
Rapid raise in testosterone over 2 years causes what?
nduces pubic hair, penile growth, sperm production, development of muscle mass and bone growth leading to linear growth (10.5-17.5)
Estrogen during puberty is responsible for what?
GH increase (subsequent IGF-I increase) mainly due to gonadal estrogen, estrogen blocker in males blocks growth and 5aDHT has no effect, estrogen induces transient resistance of HPaxis to negative feedback of GH and IGF at onset of puberty
Where are the leydig cells found? What do they do?
in intertubular space surrounded by CT, secrete E2, LH sensitive, androgen producing (Granulosa counterpart)
What are the 6 stages of spermatogenesis? How long does it take?
primary spermatogonium, secondary spermatogonium, primary spermatocyte, secondary sermatocyte, spermatid and spermatozoon; 70 days
What is the make-up of the blood testes barrier?
adjacent sertoli cells, forma tight junction around spermatogonium; spermatogonial cells moving divide tubular wall into basal and adluminal compartments
What occurs during spermiogenesis? What is the product?
spermatids attach to abutting sertoli cells penetrate into cytoplasm and undergo metamorphosis; spermatozoa; cytoplasm shrinks, chromosome condense, acromsome sac appears on apical side of nucleus and flagellum developsspermatozoa are transported into epididymis by spermiation
how do the sertoli cells regulate spermatogenesis?
produce AMH during fetal life and inhibin and ABP after puberty
how do leydig cells regulate spermatogenesis?
express 17B-hydroxysteroid dehydrogenase type 3 and aromatase and produce testosterone, growth factors and estradiol-17B
What LH induced gynecomastia?
hyperstimulation of 17BHSD3 and aromatase activites in leydig cells by LH results in over production of E-17B (60-70% of adolescent boys
What is the function of FSH in puberty?
maintains sertoli function and essential for intitiation of spermatogenesis
What does LH do during puberty?
maintains Leydig cell activities; CYP19 induction (E2 from T)
What is the function of T in spermatogenesis?
vital for completion of meiosis of primary spermatocytes
What is the pathway for T synthesis in leydig cells?
cholesterol to pregnenolone by CYP11A1, pregnenolone to progesterone via #BHSD; Progesterone to 17OH-Progesterone via CYP17 then to androstenedione via CYP17; 17BHSD to get T
What target tissues reduce testosterone? To What by what enzyme?
prostate, seminal vesicles, genital area skin, brain, hair follicles5a-reductase in Peripheral tissues to get DHT
how does T self regulate?
controlling activity of CYP enzymes; controls rate of synthesis
Hi0w do T and 5a-DHT travel in the blood?
SHBG and ABP
How does male reporoductive function change with age?
leydig cell response to LH declines at 70-80, plasma T levels decline; administering T exogenously can lead to increased cancer rates
What does 5a-DHT do by itself in embryonic life?
labioscrotal fushion, Normal phallic development
What does 5a-DHT do by itself in pubertal development?
male pattern hair distribution (mustache, beard, chest hair)
What does 5a-DHT do by itself in adult life?
development of BPH
What does 5a-DHT and T do in embryonic development?
proper prostatic development, phallic growth, testicular descent
What does 5a-DHT and T do in Pubertal development?
ambisexual hair growth, activity of sebaceous and apocrine sweat glands, penile erection, feedback regulation of gonadotropin secretion
What does 5a-DHT and T do in adult life?
male pattern baldness, erection
What does T do in embryonic development?
epididymis, Vas, seminal vesicles
What does T do in pubertal development?
erythropoiesis, muscle growth, growth of male sex organs, behavioral responses (libido, aggression, sexual orientation toward females) laryngeal growth, upper body fat
What does T do in adult life?
erythropoiesis, muscle growth, behavioral responses (libido, aggression, sexual orientation toward females), decreased HDL, spermatogenesis, inhibition of breast development
What does E2 do in pubertal development?
What does E2 do in adult life?
prevention of osteoporosis, prevention of alzheimers (maybe), fluid retention, feedback regulation of gonadotropin secretion
how can breast development occur in males?
increased FSH and LH due to blocked negative feedback, testis stimulation, increased testosterone, converted to E2
What occurs during erection?
perineal stimulation or arousal-> PS discharge-> arterial dilation due to ER of NOand constriction of veins in cavernosa-> increased blood accumulation
What is composition of semen?
vas contents spermatozoa and watery fluid, P(20-30%) citric acid, zinc, and acid phosphatase, Seminal vesicle secretion (60%) fructose and PG
how does ejaculation occur?
sympathetic discharge->rhythmic contraction of vas, SV and penile urethra-> seminal discharge
What are the causes of pseudohermaphroditism?
testicular dysgenesis (associated w/ renal disease), disorders of androgen synthesis ( leydig hyperplasia, abnormal cholesterol transport, or deficiencies of steroidogenic enzyme activity-5a-reductase), abnormal androgen receptor function (full or partial; AMH degeneration of upper MD but A does not work on lower-blind vaginal pouch), maternal E or P, persistent MD syndrome (AMH defect), and vanishing testes syndromes
What is cryptorchidism? prevalence of types?
failure of testicular descent; give rise to tumor, defective spermatogenesis (can be recovered, type a and B spermatagonium present) intraabdominal (10%), canalicular testis (20%)- smaller and palpable, high scrotal (40%), obstructed testis (30%
What are the causes of hypogondaotropic hypogonadism?
Kallman (absenceGnRH, deficient androgenization, microcephallus, cryptorchidism, often Prader willi associated, short stature and MR) and hyperprolactinemia (micro or macroadenoma of pituitary secreting PRL, interferes with LHRH leading to impotence
What is peripubertal hypogonadism? (eunuchoidism) symptoms?
longer time for long bone growth before epiphyseal closure, lower segment > than upper, female type fat distribution including gynecomastia, body hair including female pubic hair pattern, failure of laryngeal growth, decreased muscle strength, no male pattern baldness
What are the symptoms of post-pubertal hypogonadism?
no acne, decreased shaving frequency, decreased libido, impotence, failure of male pattern baldness, fine wrinkling of skin, small testes
What causes BPH? Treatment?
DHT acting via androgen receptors stimulates growth of prostate epithelium; GnRH antagonist, reduces T production which decreases 5a-DHT leading to shrinkage of prostate
What are some organic causes of impotence?
endocrine disorders leading to decreased/loss of T production or action, cirrhosis of liver, diabetic neuropathy, psychotropic drug, anti prostate cancer drugs, systemic illness, trauma or radiation