Male Repro. Phys Flashcards
How do FSH and LH relate to each other during male childhood, adult hood, and senescence?
Childhood: FSH >LH Adult: LH>FSH Senescence: FSH >LH
What stimulates puberty?
Pulsatile secretion of GnRH and pulsatile secretion of FSH and LH
What are responsible for secondary sex characteristics?
Increasing levels of sex steroid hormones
What is the seminiferous tubule epithelium formed from?
Sertoli cells interspersed with germ cells such as spermatogonia and spermatozoa
Where are leydig cells found?
Interstitial cells btw tubules
80% of the adult testis is made up of ___ and 20% is ___/
Seminiferous tubules and CT interspersed with Leydig cells
Sertoli cell functions?
Provides nutrients to the developing sperm. Forms tight jxn creating BTB Secretes aqueous fluid into lumen of seminiferous tubules for sperm transport
Leydig function?
Synthesis and secretion of testosterone
compared to adrenal cortex, what enzymes are testis lacking?
21-b hydroxylase and 11-b hydroxylase
What enzyme do the testes have that converts androstenedione to testosterone?
17B Hydroxysteroid dehydrogenase
Where is testosterone concentrated and how?
In the lumen of the seminiferous tubules and by binding to ABP
what enzyme is key for peripheral tissues to convert Testosterone to DHT?
5a reductase
Which hormone Testosterone or DHT has greater affinity for androgen receptors?
DHT
What happens if there is deficiency of 5a reductase?
ambiguous external genitalia
In male reproductive tract, where are estrogen levels highest? How is it produced?
In the seminiferous tubules fluid, it is produced from sertoli cells from conversion of testosterone to estradiol mediated by aromatase (CYP19)
Where are large amounts of estrogen found in the male body?
Adipose tissue
Describe the mitochondrial pathway for testosterone synthesis.
- Cytochronme P450 SCC (desmolase) cleaves side chain on cholesterol to convert it to pregnenolone
- Rate limiting step is converwsion of cholesterol to prenenolone
Where does testosterone go from the leydig cells?
- Diffuses into seminiferous tubules and into peritubular capillary network to be carried to peripheral circulation
How can leydig cells make cholesterol?
- Synthesize denovo via taking up LDL from circulation and HDL
- Can also store cholesterool as cholesterol esters
- Free cholesterol is made in testis leydig cells via HSL
- HSL converts cholesterol esters to free cholesterol for androgen production
- Cholesterol is transferred in mito membranes via StAR
- Converted to pregnenolone
- Free cholesterol is made in testis leydig cells via HSL
What three ways are testosterone transported?
- 60% bound to sex hormone binding globulin
- 38% bound to albumin
- 2% free, which is the active biological form
How does testosterone leave the body?
Excreted in urine:
- 50% of excreted androgens are found as urinary 17-ketosteroiods
- remander are conjugated androges or diol triol derivitves
When is testosterone present in fetal life?
- Present in second month of embryonic life
- It will determine if penis and scrotum develop
- if lacking testosterone clitoris and vagina form
What does testosterone do in fetal life?
- Fetal differentiation of internal male reproductive tact
- Epididymis, vas deferens and seminal vesicles
- Causes descent of testes into scrotum during last 2-3 months of pregnancy
Testosterone actions at puberty?
- Increase mm mass
- Pubertal growth spurt
- Closure of epiphyseal plate
- Growth of penis and seminal vesicles
- Deepening of voice
- Spermatogenesis
- Libido
What are the specific actions of DHT?
Important for fetal differentiation of external male genitalia
- also important for male hair distribution, sebaceous gland activity and growth of prostate
What enzyme inhibitor can be used for treatment of benign prostatic hypertrophy and hair loss in males?
- 5a reductase inhibitor, this works bc DHT is responsible for prostate growth and male pattern baldness. This enzyme converts testosterone into DHT
What are the anabolic actions of adrogens? (7)
- Stimulates erythropoietin synthesis
- Stiulates sebaceous gland secretions
- Controls protein anabolic effects (nitrogen retention)
- Stimulates linear bone growth and closure of epiphyses
- Stimulates ABP synthesis
- Maintenance of secretions of sex glands
- Regulation of behavioural effects including libido
What is benign prostatic hyperplasia (BPH) and sx?
- Increased growth of the prostate gland
- Concentrations of DHT in prostatic tissues aren’t higher than in men without BPH, although they may have more DHT receptors on their prostate
- Urinary frequency urgency and nocturia, difficulty initiating and maintaining a stream, feeling fullness in bladder, dribbling of urine
What does the leydig cell -LH receptor path result inn?
cAMP PKA pathway
- results in steroidogenesis and testosterone production
- Testosterone diffuses into seminiferous tubules and periphieral circulationn
What stimulates Sertoli cells and what is the pathway and result?
- Stimulated by FSH and testosterone
- cAMP PKA path
- Results in protein synthesis and production of ABP,aromatase and inhibin which inhibits FSH release,
How do sertoli cells and testosterone relate?
- FSH stimulates sertoli cells to secrete ABP into the lumen of seminiferous tubules
- Binding of tewstosterone in thel ume provides local testosterone supply for developing spermatogonia
What are the supportive functions of the sertoli cells?
- Maintains BTB
- Phagocytosis
- Transfer nutrients from blood to sperm
- Reeptors for hormones and paraccrines
What are the exocrine functions of the sertoli cells?
- Productionn of fluid
- Production of ABP
- Determines release of sperm from seminiferous tubules
What are the endocrine functions of sertoli cells?
- Esxpression of ABP T and FSH receptors
- Production of AMH
- Aromatization of testosterone to estradiol
- Production of inhibin to regulate FSH
What cells do LH stimulate in males?
Leydig cells to produce testosterone which eventually has negative feedback to the anterior pit and hypothalamus
what cells are stimulated by FSH?
- Sertoli cells to produce ABP, estrogens, spermatogenesis, and inhibin
- Eventually NFB to anterior pit
What are the three phases of spermatogenesis?
- Mitotic divisions
- Meiotic division
- Spermiogenesis
What happens during the mitotic divisions of spermatogenesis?
- Proliferative phase
- At puberty the mitotic cycles will increase and spermatogonia or stem cells will divide to produce daughter cells
- After the last division we have primary spermatocytes
What happens during meiosis of spermatogenesis?
-
Primary spermatocytes undergo two meiotic divisions
- first one yields two secondary spermatocytes each witha haploid number of duplicated chromosomes
- Secondary spermatocytes enter a seconde meiotic divison producing two spermatids each with a haploid number of unduplicated chromosomes
What is spermiogenesis of spermatogenis cycle?
- Spermatids undergo spermiogenesis and mature into spermatozoa
- Nuclear and cytoplasmic changes produce mature spermatozoa
- ends in testis with release of spermatozoa from sertoli cells
where are mitochondria found in the sperm
Middle piece
What hormone must be secreted to stimulate spermiogenesis?
FSH as it stimulates sertoli cells to nurse and form sperm
Why is GH important in spermatogenesis?
- It regulates the metabolic functions of the testes
- It promotes early divison of sperm
- If it is lacking spermatogenesis is sseverely deficient or absent leaving the patient infertile
How does administration of exogenous testosterone affect spermiogenesis?
Disrupts the hypothalamic pituitary axis, the exogenous testosterone can negatively feeback on the hypothalamus resulting in decrease of LH and FSH which will decrease Tesstosterone levels therefore decreasing spermatogenesis
After being released from the rete testis where do sperm go and how long are they there?
Epididymis for ~1 month or further maturation
Where does decapacitation occur?
- In the epididymis
- involves adding molecules to membranes of the sperm
What do the seminal vesicles do?
Secrete mucoid fluid with nutrients and prostaglandins and fibrinogen
- adds significant amount of nutrient value to ejaculated sperm
- Prostaglandins help with fertilization as it thins the cervical mucus and causes backward reverse peristaltic contractions in thhe uterus fallopian tubes to move ejaculated sperm to the ovaries
What does the prostate gland do?
- Secretes thin milky fluid wit hCa citrate and phosphate clotting enzymes and profibrinonlysin
- Slightly alkaline and helps neutralize the acididty of other seminal fluids during ejaculation and enhancnes motility and fertility of sperm
What is semen composed of?
- Fluid and sperm from vas deferens and fluid from seminal vesicles, prostate and bulbourethral glands
- pH 7.5
What is sperm cell life span onnce ejaculated and what is considered infertile levels of sperm?
- 24-48 hours at body temperature
- Each ejaculation should contain 2-6 mL with 20-200 million sperm
- less than 20 million is infertile
What makes up the erectile tissues?
- 2 Corpora cavernosum
- 1 corpus spongisoum
- made of anastomosingn network of potential cavernous vascular spaces lined with continnuous endothelia within a loose CT support
What happens during erection?
- Parasympathetic nerves innervate vascular sm mm of the helicine arteries which supplies the blood to the cavernous spaces in the erectile tissue and releases NO
- NO will activate GC increasing cGMP decreasing intracellular calcium resulting in relaxationn of vascular sm mm
- Vasodilation allows blood to fill the spaces causing engorgement and erection
- The enlarged tissue pushes the veins against the outer fascia reducing venous drainage
- Somatic stimulation increases contractions of muscles at base of penis further promoting the erectionn
What happens during emission? What is emission?
- Movement of semen from epididymis vas deferens seminal vesicles and prostate to ejaculatory ducts
- Under sympathetic control
- Causing sequential peristaltic contractions of the sm mm of vas deferens and closing internal sphinncter of the bladder
- emission precedes ejaculation but also continnues during ejaculation
What happens if the internal sphincter of the bladder is destroyed during a prostatectomy?
Retrograde ejaculation
What happens during ejaculation?
- Caused by rhythmic contraction of bulbospongiosus and ischiocavernosus muscles surrounding the base, innervated by somatic nerves
- Contraction causes semen to exit quickly out the urethra
What is capacitation of spermatozoa?
- uterine and fallopian tubes wash away inhibitory factos
- Loss of the cholesterol on the acrosome allowing acrosomal rxn to occur
- Membrane of sperm is more permeable to Ca inicreasingn the motility of sperm
What happens if testosterone is deficient during the 2nd -3rd month of gestation?
Ressults in varying degrees of ambuiguity in male genitalia
Wha happens if testosterone deficiency in third trimester of pregnancy?
Problems with testicular descent along with micropenis
what happens if deficient in testosterone at puberty?
Leads to poor secondary sexual development and overall eunuchoid features
What happens if you are deficient in testosterone post puberty?
Leads to decreased libido erectile dysfunciton decrease facial and body hair growth low eneregy and infertility
what is kallman’s syndrome?
Genetic dissorder that occurs when GnRH neurons fail to migrate to hypothalamus during embryonic development
- delayed or absent puberty and imparied sense of smell
- Form of hypogonadotropic hypogonadism
- Occurs more in males
Klinefelter syndrome?
- Seminiferous tubular dysgenesis individeuals will have 47 XXY
- Phenotypically male due to Y chromosome
- At puberty increased levels of gonadotropins dont induce normal testicular growth and spermatogenesis
- Androgen production is low where levels of gonadotropins are elevated indicating primary hypogonadism
- Seminniferous tubules are destroyed resulting in infertility
Patient labs show decreased testosterone secretioni and testicular dysfunction, what is the issue?
Primary hypogonadism, Klinefelter’s syndrome
Decreased testosterone and increased LH
If there is a pituitary dysfunction such as a turmor, and LH FSH secretion are decreased what results?
Secondary hypogonadism, decreased testosterone or decreased/normal LH
How do you treat BPH?
5a reductase inhibitor, decreasing DHT
a man and his wife present to fertility clinic bc they haven’t been able to get pregnant for a year. Husband is tall and thin, has sparse axillary and pubic hair, decreased mm mass, small testes, and gynecomastia. His urinary gonadotropin levels are elevated and analysis of sperm reveals azoospermia. What is likely the diagnosis?
Klinefelter syndrome
- no sperm are produced due to destroyed seminiferous tubules
- small testes
What can treat prostate cancer?
Androgen receptor atagonist, radiotherapy radical prostatectomy
What occurs with tumors in the testis?
production of large amounts of testosterone
What do germminal epithelial tumors produce?
no hormones
What is andropause?
- Gonadal sensitivity to LH decreases and androgen production drops as men age
- Serum LH and FSH levels will rise as testosterone levels are decreased
