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Physiology Unit 7 > Male Repro Endodrinology > Flashcards

Male Repro Endodrinology Flashcards

1
Q

genotypic sex

A
  • Y chromosome

- y makes male (?)

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2
Q

gonadal sex

A
  • SRY gene encodes testis determining factor
  • TDF is a TF
  • SRY causes testes and germ cells develop into spermatogonia
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3
Q

phenotypic sex

A
  • hormones produced by the gonads determine phenotypic sex
  • development of accessory sex organs
  • external genitalia
  • requires DHT
  • secondary sex characteristics
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4
Q

XX male

A
  • in rare cases, SRY gene translocates to the X chromosome during male meiosis
  • the ovum receiving the X chromosome with the SRY gene with develop into a male
  • 1 in 100,000 live births
  • no normal testes
  • sperm can also carry Y with no TDF, causes XY female
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5
Q

differentiation of the testes

A
  • primordial gonad contains the germ cells
  • genotype of germ cells determines fate of the gonad
  • considered indifferent before it differentiates into testes or ovary
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6
Q

androgens

A
  • produced by leydig cells
  • promote differentiation of the wolffian duct and prostate development
  • anti-mullerian hormone from sertoli cells causes mullerian ducts to degenerate
  • wolffian duct requires testosterone, prostate DHT
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7
Q

wolffian duct

A
  • becomes vas deferans, seminal vesicles, ejaculatory duct

- internal genitalia

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8
Q

mullerian duct

A

-fallopian tubes, cervix, uterus

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9
Q

DHT 1

A

causes differentiation of external genitalia in males

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10
Q

homologous regions of male and female external genitalia

A
  • testosterone to DHT stimulates male external genitalia
  • 10 weeks of gestation
  • lots of homology
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11
Q

hypothal-pit-gonadal axis (male)

A
  • regulates spermatogenesis and androgen production
  • GnRH is pulsatile
  • LH and FSH is pulsatile
  • constant levels of GnRH prevents LH and FSH release
  • products of the testes have a negative feedback on hypothal and ant pit
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12
Q

GnRH

A
  • synthesized as a 69 residue prohormone by small bodied petidergic neurons in the arcuate nuclei and secreted into the portal blood vessels
  • cleaved to a 10 aa hormone
  • binds Gq and activates PLC and increases, Ca, DAG and PKC
  • constant supply downregulates receptors and fails to induce LH or FSH secretion
  • used to treat prostate cancer to lower testosterone production
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13
Q

pre-natal axis

A
  • leydig cells (sex steroid production) make up more than half of the testes by 60 days of gestaion
  • increase in leydig cells is dependent on maternal hCG or embryonic LH
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14
Q

prior to puberty

A
  • few GnRH pulses and low FSH and LH
  • hypothal and pit very sensitive to negative feedback inhibition by androgens
  • spermatogonia exist in diploid, undifferentiated form in basal component of testes
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15
Q

puberty

A
  • freq and amp of GnRH pulses increase
  • sensitivity of HP axis to negative feedback decreases
  • gonadotroph sensitivity to GnRH increases
  • LH and FSH production increases
  • testosterone increases and spermatogenesis begins
  • androgen driven changes characteristic of puberty occur
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16
Q

LH

A
  • leydig cells, La testosterone
  • neg feedback on ant pit and hypothal
  • testosterone has pos effect on sertoli cells
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17
Q

FSH

A
  • has S- sertoli cells
  • inhibin
  • neg feedback on ant pit
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18
Q

physiology of the leydig cells

A
  • LH binds
  • activates Gs
  • increases PKA
  • new protein synthesis
  • increased use of cholesterol
  • increased production of testosterone
  • which then goes out through sertoli cells to the lumen
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19
Q

physiology of sertoli cells

A
  • FSH binds
  • activates Gs and PKA
  • increases new protein synthesis
  • increases inhibins, ABP (keeps local testosterone high), aromatase, and GF
  • GF diffuse to leydig
  • aromatase increases synthesis of estradiol from testosterone, which diffuses to leydig cell
20
Q

cross-talk between leydig and sertoli cels

A
  • leydig–>testosterone–>sertoli cells
  • leydig–>B-endorphin–>inhibit sertoli cell proliferation
  • sertoli cells–>estrogen–> leydig cells
  • sertoli cells–>GF–> increase LH receptor on leydig cells
21
Q

Kallmann Syndrome

A
  • hypogonadotropic hypogonadism
  • caused by mutations in KAL-1 (x), FGFR1 (AD), PROK2 and PROKR2
  • fail to enter puberty and can’t smell
  • lack LH and FSH
  • agnoesis of the olfactory lobes
  • 1/10,000 males, 15,000 females
  • developmental origin of odor receptor cells and GnRH cells is the same
  • both develop in olfactory epithelium
  • primary neurosensory cells extend axons into the olfactory bulb and GnRH cells migrate along axons into brain and hypothal
  • main danger is osteoporosis
22
Q

androgen synthesis

A
  • cholesterol to pregnenolone by desmolase in mitochondria, up-regulated by LH
  • testosterone to DHT by 5-a-reductase (leydig cells)
  • androstenedione and testosterone to estrone and estradiol by aromatase in sertoli cells
23
Q

male pseudohermaphroditism

A
  • any deficit by which androgens act in genetic males may cause this syndrom
  • 5a reductase deficiency
  • DHT reduces, testosterone ok
  • failure of DHT dependent development- urogenital sinus and external genitalia
24
Q

androgen insensitivity syndrome

A
  • another cause of male pseudohermaphroditism
  • normal levels of testosterone and DHT
  • androgen receptors are absent or defective
  • urogenital sinus and external genitalia develop according to female pattern, wolffian ducts degenerate
  • normal levels of AMH suppress mullerian development
25
Q

androgen actions

A
  • affect nearly every tissue in the body

- classified as androgenic or anabolic

26
Q

androgenic effects of androgens

A
  • maturation of the sex organs, particularly the penis
  • development of secondary sexual characteristics
  • deepening of the voice, growth of the beard, axillary hair
27
Q

anabolic effects of androgens

A
  • promote protein synthesis and growth of tissues expressing androgen receptors
  • growth of muscle and increase in strength
  • increase in bone density and strength, linear growth and maturation
  • males have larger hears, lungs, liver, erythrocytes, etc
  • bone maturation occurs indirectly through estradiol metabolites and is more gradual in men than women
  • men have a larger brain but women have a more dendritic connections
28
Q

androgen’s effect on organs

A
  • FSH levels 8x higher
  • male pattern of gonadotropins regulated by combined action of E2, T, DHT
  • increase expression of erythropoietin from kidneys, higher crit
  • paradoxically, estrogens regulate male sexual behavior
  • men have 20-40% more muscle mass than females
  • penis, seminal vesicles, and prostate increase in size during puberty
  • dependent upon DHT
29
Q

plasma testosterone vs age

A
  • lots during development
  • spike before one year
  • increases at puberty and decreases after senescence
30
Q

andropause

A
  • unlike menopause
  • no abrupt loss of fertility
  • testosterone decreases with age especially over 40
  • quantity and quality of sperm decrease
  • FSH and LH levels increase
  • reduced testosterone causes some of the problems of aging- decreased bone formation, muscle mass, appetite, libido, blood hematocrit
  • fall by 10% per year beginning in the 30s, but mid 50s 30% of men experience
31
Q

low testosterone

A
  • small percentage of men have levels below 300
  • sx- low sex drive, erectile dysfunction, loss of muscle mass, mood problems, fatigue, sleep disturbances, loss of body and facial hair
  • high percentage of men with sx will benefit from trt
  • men with prostate of breast cancer shouldn’t have testosterone
32
Q

finasteride

A
  • propecia
  • blocks production of DHT, used to treat male pattern baldness
  • side effects- impotence, abnormal ejaculation, depression

testosterone:

  • can worsen sleep apnea, BPH, CHF or high RBC counts
  • too much can increase chance of prostate cancer
  • hair loss
33
Q

effects of anabolic steroid abuse

A
  • anabolic steroids abused by individuals attempting to increase muscle mass or gain a competitive advantage can lead to the following:
  • reduced sperm count, shrinkage of testicles (desensitization, no LH b/c neg feedback)
  • permanent damage to heart liver, kidneys, psychiatric probs
  • irreversible breast enlargement in men
  • woman and girls can develop excessive body hair and deepening of the voice
  • premature heart failure, HTN, liver tumors, stroke, kidney failure
  • increase in LDL and decrease in HDL
  • HIV and hepatitis if needles reused
34
Q

kennedy’s disease

A
  • spinobulbar muscular atrophy
  • LMN disease caused by mutation in androgen receptor
  • expansion of CAG repeat in gene causes a polyglutamine expansion in androgen receptor
  • mutation in receptor causes toxic gain of function
  • patients display progressive weakness due to degeneration of motor neurons in brain stem and spinal cord
  • X linked
  • weakness of tongue and mouth muscles, fasiculations and progressive weakness of the limbs
  • muscle wasting in middle age
  • onset related to size of polyglutamine expansion
35
Q

sertoli cells and sperm

A
  • spermatogenesis is initiated at puberty through FSH and LH
  • sertoli cells support with GFs
  • FSH activates sertoli cells to make sperm
  • also supported by LH driven increases in testosteone
36
Q

spermatozoa development

A
  • primary (diploid, 4N), meiosis I, secondary are haploid and 2N
  • meiosis II
  • haploid and 1 N=spermatids
  • then through spermiogenesis to spermatozoa
37
Q

sperm maturation

A
  • after spermiation, spermatids move passively into rete testis and epididymis
  • testosterone dependent maturation requires for fully mobile/fertile sperm
  • total process about 70 days
  • after sperm are ejaculated, several changes, which activates them
  • during capacitation the sperm becomes hyperactive
  • acrosome provides protection and carries enzymes necessary for acrosomal reaction that dissolves jelly coat of the egg
  • mito for E
38
Q

accessory male sex glands

A
  • produce seminal plasmi
  • semen is only 10% sperm
  • seminal fluid contains a plethora of sugars and ions
  • derived from seminal vesicles, prostate gland, bulbourethral glands
  • seminal vesicles provide 70% of volume and fructose
  • normal concentration > 20 million sperm/ml
39
Q

erection, emission, ejaculation SNS

A
  • fibers from T11-L2
  • reach genitals via inferior mesenteric, hypogasteric and pelvix plexi
  • hypogastric and cavernous nerves
  • responsible for emission and ejaculation
  • SNS tone maintains detumescence
40
Q

PNS

A
  • fibers from S2-4
  • pelvic nerve to pelvic plexus
  • post gang fibers reach penile corpora and vasculature via cavernous nerves
  • responsible for corporeal vasodilation and smooth muscle relaxation leading to erection
41
Q

somatic innervation

A
  • fibers via pudendal nerve to striated muscle of penis
  • sensory afferent fibers carried mainly in the dorsal nerve of the penis reach the sc via pudendal nerve
  • compression can lead to temporary sexual dysfunction
42
Q

ACh and NO

A
  • PNS gives ACh to endo cells
  • NO to cGMP increases vasodilation
  • phosphodiesterase inhibits cGMP and erection, viagra inhibits phosphodiesterase (during arousal, blue vision)
  • NO relaxes smooth muscle and leads to vasodilation
  • decrease in SNS tone allows for relaxation of smooth muscle
  • ACh acts through M3 receptors on endo cells to produce NO
43
Q

mechanics of erection

A
  • PNS fibers in cavernous nerve cause dilation of arteriolar smooth muscle
  • decrease in SNS tone to vascular smooth muscle
  • increased blood flow to corpora
  • increased somatic fiber stimulation results in striated muscle contraction causing decreased venous outflow
  • sinusoids or corpora expand and cause erection
44
Q

emission

A
  • movement of ejaculate into urethra
  • SNS stimulation of hypogastric nerve causes contraction of smooth muscle of distal epididymis, vas deferens, and accessory glands
  • semen propelled into prostatic urethra
  • internal sphincter of bladder prevents retrograde flow of sperm
45
Q

ejaculation

A
  • spinal reflex
  • often accompanied by orgasm (CNS)
  • expulsion of sperm from urethra
  • rapid spinal reflex stimulated by entry of semen into bulbous urethra
  • mediated by S2-4 and somatic motor fibers in pudendal nerve
  • initiates rhythmic contractions of the striated muscles of the perineal area
46
Q

anejaculation

A
  • pathological inability to ejaculate due to:
  • sexual inhibition
  • pharmacological inhibition
  • ANS malfunction
  • prostatectomy
  • ejaculatory duct obstruction

Physiology Unit 7 (10 decks)

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