Male Repro Phys Flashcards
How is puberty initiated?
Pulsatile secretion GnRH
Which drive pulsatile secretion of FSH and LH
Which stimulates secretion of gonadal steroid hormones, testosterone, and estradiol
Increased circulating levels of sex hormones responsible for appearance of secondary sex characteristics at puberty
What may be a natural inhibitor of GnRH release? Describe
Melatonin
Secreted by pineal gland
Levels are highest during childhood and decline in adulthood
Removal of pineal gland precipitates early puberty
What are the main functions of testes?
Spermatogenesis
Secretion of testosterone
Describe function of scrotum
Lower temperature essential for spermatogenesis (1-2 degrees C below body temp)
Describe function of epididymis
Primary location for maturation and storage of sperm
Describe function of vas deferens
Another storage area (ampulla) for sperm
Secretes fluid rich in citrate and fructose
Describe function of seminal vesicles
Secretes fluid rich in citrate, fructose, prostaglandins, and fibrinogen
Describe function of prostate gland
Secretes milky aqueous solution rich in citrate, calcium, and enzymes, phosphate ion, clotting enzyme, profibrinolysin
Describe epithelium of seminiferous tubules
Formed by Sertoli cells with interspersed germ cells
Describe spermatogonia
Most immature germ cells
Located near periphery of tubule
Describe spermatozoa
Mature germ cells
Located near lumen of tubule
Where are Leydig cells?
Interstitial cells that lie between tubules
What are the functions of Sertoli cells?
Provide nutrients for differentiating sperm
Form tight junctions with each other, creating a barrier between testes and bloodstream
Secrete aqueous fluid into lumen into seminiferous tubules to help transport sperm through tubules into epididymis
What cells provide nutrients to differentiating sperm, form tight junctions (blood-testes barrier), and secrete aqueous fluid into lumen of seminiferous tubules?
Sertoli cells
Describe the blood-testes barrier
Formed by tight junctions by Sertoli cells
Imparts selective permeability
Admits certain substances to cross (testosterone) but prohibits noxious substances
What are the main functions of Leydig cells?
Synthesis and secretion of testosterone
Main steroidogenic cells
What cells synthesize and secrete testosterone?
Leydig cells
Describe fetal Leydig cells
Responsible for masculinizing male urogenital tract and inducing testis descent
Cells atrophy shortly after birth and do not contribute to adult Leydig cell population
Describe adult Leydig cells
Derived from undifferentiated precursors present after birth and become fully steroidogenic at puberty
How do Leydig cells acquire cholesterol, and what does it convert cholesterol to?
Acquire cholesterol from circulation, through low-density lipoprotein (LDL) receptors
To a lesser extent, through high-density lipoprotein (HDL) receptors
Cholesterol is converted to pregnenolone
How do Leydig cells store and transfer cholesterol?
Store cholesterol as cholesterol esters
Free testosterone is generated within Leydig cells by cholesterol hormone-sensitive lipase (HSL)
HSL converts cholesterol esters to free cholesterol for androgen production
Cholesterol is then transferred within mitochondrial membranes via steroidogenic acute regulatory protein (StAR)
What enzyme do testes lack?
21 beta-hydroxylase
11 beta-hydroxylase
So not glucocorticoids or mineralocorticoids are synthesized
What enzyme does testes have?
17 beta-hydroxysteroid dehydrogenase
What does 17 beta-hydroxysteroid dehydrogenase do?
In testes
Converts androstenedione to testosterone
In testes, what converts androstenedione to testosterone?
17 beta-hydroxysteroid dehydrogenase
Where and how is testosterone concentrated?
In lumen of seminiferous tubules
Concentrated by binding to androgen-binding protein (ABP)
What does androgen-binding protein (ABP) in seminiferous tubules do?
Concentrate testosterone
In peripheral tissue, what converts testosterone to dihydrotestosterone (DHT)?
5alpha-reductase
In peripheral tissues, what does 5alpha-reductase do?
Converts testosterone to dihydrotesosterone
What is most circulating testosterone bound to?
Sex hormone-binding globulins (SHBG)
Albumin
What do sex hormone-binding globulin (SHBG) and albumin do?
Binds circulating testosterone
Most estrogen in males is produced by liver. What else might be a source of estrogen?
Sertoli cells
Conversion of testosterone to estradiol mediated by aromatase
Describe the mitochondrial pathway for testosterone synthesis
Cytochrome P450 side-chain cleavage enzyme removes side-chain from carbon at position 20 of cholesterol
AKA cholesterol desomolase
What is the rate-limiting step in synthesis of testosterone?
Conversion of cholesterol to pregnenolone
What does steroidogenic acute regulatory protein (StAR) do?
Transfer cholesterol from inner to outer mitochondrial membrane
What stimulates conversion of cholesterol to pregnenolone and regulates overall rate of testosterone synthesis by Leydig cell?
LH
What does LH do to Leydig cell?
Stimulates conversion of cholesterol to pregnenolone
Regulates overall rate of testosterone synthesis
How does LH promote pregnenolone synthesis?
Increase affinity of P450scc (cholesterol desmolase) enzyme for cholesterol
Long-term action in which it stimulates synthesis of P450scc enzyme
What increases synthesis of and affinity of P450scc (cholesterol desmolase) for cholesterol?
LH
What does aromatase do?
Converts testosterone to estradiol
What converts testosterone to estradiol?
Aromatase
What are the actions of testosterone during fetal development?
Penis and scrotum
Differentiation of internal male genital tract (epididymis, vas deferens, and seminal vesicles)
Causes descent of testes into scrotum during last 2-3 months
What are the actions of testosterone during puberty?
Increased muscle mass Pubertal growth spurt Closure of epiphyseal plates Growth of penis and seminal vesciles Deepening of voice Spermatogenesis Libido
What are the actions of DHT?
Fetal differentiation of external male genitalia (penis, scrotum, and prostate)
Male hair distribution and male pattern baldness
Sebaceous gland activity
Growth of prostate
What can be used as treatment for benign prostatic hypertrophy and hair loss in males?
5alpha-reductase inhibitors
Describe the androgenic actions of androgens
Regulation of differentiation of male internal and external genitalia in fetus
Stimulation of growth, development of secondary sexual characteristics at puberty
Maintenance of reproductive tract and production of sperm
Initiation and maintenance of spermatogenesis
Describe the anabolic actions of androgens
Stimulation erythropoietin synthesis (stimulates red blood cell production)
Stimulation of sebaceous gland secretion
Control of protein anabolic effect (nitrogen retention)
Stimulation of linear body growth, bone growth, and closure of epiphyses
Stimulation of androgen binding protein synthesis
Maintenance of secretions of sex glands
Regulation of behavioral effects, including libido
What is the LH receptor pathway coupled to?
CAMP-PKA pathway
Results in steroidogenesis and testosterone production
What is FSH receptor coupled to?
CAMP-PKA pathway
Involved in protein synthesis and production of inhibin, which inhibits FSH release
What stimulates Sertoli cells to secrete ABP into lumen of seminiferous tubules?
FSH
What cells does FSH stimulate?
Sertoli cells
Describe the supportive function of Sertoli cells
Maintain blood-testis barrier
Phagocytosis
Transfer nutrients from blood to sperm (transferrin, Fe, lactate)
Receptors for hormones and paracrines
Describe exocrine function of Sertoli cells
Production of fluid
Production of ABP
Determination of release of sperm from seminiferous tubule
Describe endocrine function of Sertoli cells
Expression of testosterone, ABP, and FSH receptors
Production of AMH
Aromatization of testosterone to estradiol-17beta
Production of inhibin to regulate FSH levels
What is the histology of Sertoli cells?
Tall, simple columnar cells
What are the phases of spermatogenesis?
Mitotic divisions
Meiotic divisions
Spermiogenesis
Describe spermatocytogenesis (mitotic divisions of spermatogenesis)
Proliferate phase
At puberty, mitotic cycles increase
Spermatogonia (stem cells) divide to produce daughter spermatogonia
After last division, resulting cells are called primary spermatocytes
Describe meiosis of spermatogenesis
Production of haploid gamete
Primary spermatocytes undergo two meiotic divisions
First division produces two secondary spermatocytes (haploid of duplicated chromosomes)
Secondary spermatocytes enter second meiotic division, producing two spermatids (haploid of unduplicated chromosomes)
Describe spermiogenesis (maturation in spermatogenesis)
Spermatids mature into spermatozoa
Nuclear and cytoplasmic changes
Ends in testis with release from Sertoli cells
What hormone is essential for growth and division of testicular germinal cells?
Testosterone
What stimulation is necessary for spermiogenesis to occur?
FSH stimulating Sertoli cells to nurse and form sperm
What promotes early division of sperm?
Growth hormone
Describe FSH and LH levels in childhood vs adult reproductive period vs senescence
Childhood: FSH>LH
Repro period: LH>FSH
Senescence: FSH>LH
Where do sperm undergo maturation and decapacitation?
Epididymis
How do prostaglandins from seminal vesicles aid in fertilization?
React with female cervical mucus to make to make it more receptive to sperm movement (make cervical mucus less thick)
Cause backward, reverse peristaltic contractions in uterus and fallopian tubes to move ejaculated sperm toward ovaries
What does alkaline prostatic fluid do?
Helps neutralize acidity of other seminal fluids during ejaculation to enhance motility and fertility of sperm
What is semen composed of?
Fluid and sperm from vas deferens (10%)
Fluid from seminal vesicles (60)
Fluid from prostate (30)
Small fluid amounts from mucous glands (bulbourethral gland)
What are the 3 erectile bodies in the penis?
2 corpora cavenosa
1 corpus spongiosum
Describe erection of male sexual response
Parasympathetic nerves innervating vascular SM of helicine arteries that supply blood to cavernosus spaces release NO
NO activates guanylyl cyclase, activating cGMP, which decreases intracellular Ca2+ and causes relaxation of vascular SM
Vasodilation allows blood to flow into spaces, causing engorgement and erection
Engorged tissue presses veins against a noncompliant outer fascia, thereby reducing venous drainage
Somatic stimulation increases contraction of muscles at base of penis, further promoting erection
Describe emission of male sexual response
Movement of semen from epididymis, vas deferens, seminal vesicles, and prostate to ejaculatory ducts
Under sympathetic control (adrenergic transmitter)
Causes sequential peristaltic contraction of SM of vas deferens, closing internal sphincter of bladder (prevents retrograde ejaculation) (also mediated by sympathetic adrenergic stimulation)
Emission normally precedes ejaculation but also continues during ejaculation
Describe ejaculation of male sexual response
Propulsion of semen out of male urethra
Caused by rhythmic contraction of bulbospongiosus and ischiocavernous muscles (striated muscles), which surround base of penis
Innervated by somatic motor nerves
Describe capacitation of spermatozoa
Sperm are mature when they leave epididymis, but actions are in check by secretions from genital duct epithelia
When sperm come into contact with fluids of female tract, capacitation occurs
Changes include:
Uterine & uterine tubes wash away inhibitory factors
Loss of cholesterol that had built-up on acrosome, so head of sperm becomes weaker
Membrane of sperm is much more permeable to Ca2+, increases motility of sperm
Describe sperm acrosome reaction
Hyaluronidase and proteolytic enzymes are stored in the acrosomal head of sperm
Hyaluronidase depolymerizes hyaluronic acid polymers in intercellular cement that hold ovarian granulosa cells together
Proteolytic enzymes digest proteins in structural elements of tissue cells that adhere to ovum
What happens if there is testosterone deficiency in males in 2nd-3rd month of gestation?
Varying degrees of ambiguity in male genitalia and male pseudohermaphrodism
What happens in males if there is a testosterone deficiency during the 3rd trimester of pregnancy?
Cryptorchidism (undescended testes)
Micropenis
What happens in males if there is testosterone deficiency during puberty?
Poor secondary sexual development and overall eunuchoid features
Describe eunuchoidism
Persistence of prepubertal characteristics
Often by the presence of characteristics typical of opposite sex
What happens in males if there is testosterone deficiency during post-puberty?
Decreased libido, erectile dysfunction, decreased facial and body hair growth, low energy, infertility
Describe Kallman’s syndrome
Genetic disorder
Hypothalamic neurons that are responsible releasing gonadotropin-releasing hormone (GnRH) fail to migrate into hypothalamus during embryonic development
Characterized by delayed or absent puberty and impaired sense of smell
Form of hypogonadotropic hypogonadism
Describe Klinefelter syndrome
Men with extra X chromosome
Phenotypically male and appear normal at birth
At puberty, increased levels of gonadotropins fail to induce normal testicular growth and spermatogenesis
Androgen production is usually low
Primary hypogonadism
Seminiferous tubules are largely destroyed, resulting in infertility
Describe possible andropause
As men age, gonadal sensitivity to LH decreases, and androgen production drops
Serum LH and FSH levels rise (FSH>LH)
Testosterone decreases and causes decreased bone formation, muscle mass, growth of facial hair, appetite, libido
Sperm production declines
