Male Repro Endodrinology Flashcards
1
Q
genotypic sex
A
- Y chromosome
- y makes male (?)
2
Q
gonadal sex
A
- SRY gene encodes testis determining factor
- TDF is a TF
- SRY causes testes and germ cells develop into spermatogonia
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
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
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
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
7
Q
wolffian duct
A
- becomes vas deferans, seminal vesicles, ejaculatory duct
- internal genitalia
8
Q
mullerian duct
A
-fallopian tubes, cervix, uterus
9
Q
DHT 1
A
causes differentiation of external genitalia in males
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
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
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
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
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
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
16
Q
LH
A
- leydig cells, La testosterone
- neg feedback on ant pit and hypothal
- testosterone has pos effect on sertoli cells
17
Q
FSH
A
- has S- sertoli cells
- inhibin
- neg feedback on ant pit
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
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
