Male Repro Endocrinology Flashcards
What does the SRY gene encode? What will it help transform?
Testis determining factor (TDF) Indifferent gonad becomes testes, germs cells become spermatogonia
What are characteristics of phenotypic sex?
Accessory sex organs develop; external genitalia like penis, scrotum, urethra; secondary sex characteristics
How can you have an XX male? What is this a product of?
Translocation of the SRY gene from a Y chromosome to the X chromosome of the father before the sperm fertilizes the ovum; unequal recombination event
How do you get an XY female?
If the Y chromosome from the father lacks the TDF
When is the gonad considered indifferent?
Before differentiation into testis or ovary
In males, what does the mesonephros become?
Epididymis
In males, what does the Wolffian (excretory/mesonephric) duct become?
Vas deferens, seminal vesciles, and ejaculatory duct
In males, what happens to the Mullerian/paramesonephric ducts that doesn’t happen to females?
In males, they degenerate; in females, they develop into fallopian tubes, uterus, and cervix
What causes Mallerian ducts to degenerate?
Anti-Mullerian hormone (AMH) from Sertoli cells
What do androgens made by Leydig cells promote? What does this require?
Wolffian duct development and derived structures; Testosterone!!
What does prostate development require?
DIHIDROXYTESTOSTERONE
What would lead to development of female structures?
LACK OF TESTOSTERONE!!
Besides prostate development, what does DHT regulate?
formation of male external genitalia
What word describes GnRH stimulation, and LH and FSH release?
Pulsatile!
What can prevent LH and FSH release? What can this method treat?
Constant levels of GnRH; treat prostate cancer
What does GnRH bind? What does it trigger?
GnRH receptors on gonadotrophs in AP; leads to PLC activation, IP3/DAG, and PKC activation along with IC Ca release
What kind of feedback do the products of the testes have? Where do they act?
Negative Testosterone can act on AP and hypothalamus; Inhibin only on AP (FSH)
What are Leydig cells a source of in testes? How much do they make up in testes?
Sex-steroid production; over half by 60 days gestation
What is needed to increase Leydig cells?
Maternal chorionic gonadotropin (hCG, early); embryonic leutinizing hormone (LH, late)
For males, what happens at puberty with respect to HP-gonadal axis?
- Increased number and amplitude of GnRH pulses 2. Sens to neg feedback of testosterone decreases, but more gonadotroph sens to GnRH 3. More LH and FSH production 4. More testosterone; commence spermatogenesis
What cells does FSH bind to? What is stimulated?
Sertoli cells; ABP, aromatase, growth factors, inhibin production and gene transcription
What cells does LH bind to?
Leydig cells; Involved in biosynthesis of testosterone
What does testosterone feed back on?
Hypothalamus and its release of GnRH; AP with LH release
What does inhibin feed back on?
AP and release of FSH
What does LH do at cellular level?
GPCR, make cAMP, activate PKA 1. testosterone synthesis 2. convert cholesterol to pregnenolone (stimulate) 3. help make sterol carrier protein, sterol activating protein
What does FSH do?
- Increase androgen binding protein (local testosterone kept high) 2. P450 aromatase for estrogen 3. Growth factors to support sperm production 4. Inhibins Secondary effects: Leydig cells; increase sperm motility
How do Leydig cells act on Sertoli cells?
Testosterone; beta-endorphin inhibits Sertoli cell proliferation
How do Sertoli cells interact with Leydig cells?
Estrogen; growth factors lead to increased LH receptors on Leydig cells
Where do odor receptor cells and GnRH producing cells develop?
Olfactory epithelium
How do GnRH neurons head into brain and later hypothalamus?
Along the neurosensory cell axons
What happens if GnRH neurons can’t head back to brain and hypothalamus? What is a defect? What is the main danger?
Kallmann Syndrome (hypogonadotropic hypogonadism); congenital anosmia; osteoporosis
What gene mutations can lead to Kallman Syndrome?
KAL-1 (X-linked); FGFR1 (auto dom); PROK2 and PROKR2
What is the rate-limiting step in androgen synthesis? What is it regulated by?
Cholesterol to pregnenolone through 20,22 desmolase (SCC enzyme); LH levels
What does aromatase do? Where is it located?
Conversion of androstenedione and testosterone to estrone and estradiol; Sertoli cells
How is DHT made? Where does it occur mostly?
From testosterone through 5alpha-reductase; mostly in peripheral tissues
What are two deficiencies leading to male pseudohermaphroditism?
5alpha-reductase deficiency (low DHT, okay testosterone); androgen insensitivity syndrome (normal testosterone, DHT, no androgen receptors–>Wolffian duct degen; normal levels of AMH)
What are the androgenic effects of androgens?
- Maturation of sex organs (e.g. penis) 2. Secondary sex characteristics 3. Voice deepens, beard grows, axillary hair
What are the anabolic effects of androgens?
Protein synthesis, tissue growth with androgen receptors, muscle growth, more bone density and strength; males with larger organs; estradiol can promote bone maturation
What can estrogens regulate in males?
Sex drive and behavior in males
What is the biologically active form of testosterone? What receptor does it bind? What has the higher affinity for this receptor?
Free form Homodimeric receptor (AR/AR) DHT
What does increased testosterone lead to?
Increased hematocrit, muscle mass, upper body fat, deeper voice, more LDL and VLDL; also important for Wolffian duct structures
What happens in andropause?
No abrupt loss of fertility; testosterone decreases with increased age (>40); number and quality of sperm goes down; FSH and LH increase
What problems are associated with reduced testosterone (<300 ng/dL very low)?
Less bone formation, muscle mass, appetite, libido, hematocrit; sleep disturbances, mood problems, fatigue, loss of body and facial hair
Who should not be treated with testosterone?
Men with prostate or breast cancer
What is used to treat male pattern baldness? Side effects?
Finasteride (Propecia): blocks DHT production; impotence, abnormal ejaculation, depression
What happens with anabolic steroid abuse?
- Lower sperm count, testicles shrink 2. Possible heart failure, liver tumors, stroke, kidney failure 3. Irreversible breast enlargement in men 4. women with excess body hair and voice deepening
What is Kennedy’s Disease called? What type of disease? Where is the defect? What are symptoms?
Spinobulbar Muscular Atrophy LMN disease (CAG repeat expansion leading to polyglutamine expansion in androgen receptor) Gynecomastia, impotence, erectile dysfunction
How far does a Sertoli cell cover? What connects them?
From basal lamina to seminiferous tubule lumen; tight junctions
When is spermatogenesis initiated? By what?
At puberty FSH via Sertoli cells; LH-driven increases in testosterone and Sertoli cell growth factors
What is required for fully mobile/fertile sperm?
Testosterone
What does the acrosome do for sperm?
Protection; carries enzymes needed to dissolve jelly coat of egg during fertilization
What is semen derived from? What do the seminal vesicles provide?
Seminal vesicles, bulbourethral glands, prostate; 70% of volume and fructose
What processes of the dick does the sympathetic nervous system control?
Emission and ejaculation Maintain detumescence
What does the parasympathetic nervous system control?
Erection (Tumescence)
What is responsible for penis somatic innervation? What is the blood supply of the penis?
Pudendal nerve and artery
How does erection work at a cellular level?
Nerve terminals release ACh and NO; NO relaxes smooth muscle (artery vasodilation) and increases IC cGMP levels
How does Viagra (Sildenafil) work? What are side effects?
Inhibits cGMP-specific phosphodiesterase type 5; blue vision for pilots, or taking vasodilators –> death
In terms of circulation, what enables corpora expansion?
Smooth muscle relaxation in arterial vasculature –> increased blood flow to fill and dilate sinusoidal spaces; somatic fiber stimulation and expanding cavernosal spaces decrease venous outflow (venous plexus)
What is emission? What causes it?
Ejaculate into urethra; symp stimulation causes contraction of smooth muscle in glands, epididymis, and vas deferens so semen goes into prostatic urethra
What is ejaculation? Why wouldn’t you be able to ejaculate?
Spinal reflex through pudendal nerve usually accompanied by orgasm; sex and pharmaco inhibition, ANS malfunction, prostatectomy, ejaculatory duct obstruction
