Lecture 8: Male Reproductive Physiology Flashcards
(93 cards)
1
Q
Which cells produces Antimullerian hormone and which produces testosterone?
A
Sertoli Cells = Antimullerian hormone (AMH)
Leydig Cells = Testosterone
2
Q
What is Phenotypic sex and what determines it?
A
Physical characteristics of the internal genital tract and the external genitalia; determined by the hormonal output of the gonads
3
Q
What is the Gonadotropin secretion like over a females lifetime (i.e., childhood, adult repro. period, and senescene)?
A
Childhood: FSH > LH
Adult Repro: LH > FSH (pulsatile manner)
Senescence: FSH > LH (due to decreased estrogen post-menopause)
4
Q
Why is the pulsatile secretion of FSH and LH important; especially around puberty?
A
- Stimulates secretion of gonadal steroid hormones, testosterone and estradiol
- Increased circulating levels of sex steroid hormone are then responsible for the appearance of the secondary sex characteristics at puberty
5
Q
What occurs if a GnRH analogue is administered in a pulsatile fashion vs. a long-acting version of GnRH?
A
- Pulsatile will replicate normal conditions and puberty is initiated + repro. function is established
- Long-acting will cause puberty to NOT be initiated
6
Q
What can delay the onset of puberty in girls?
A
Extreme stress or caloric deprivation
7
Q
What is the effect of Melatonin on GnRH; when are levels of melatonin highest?
A
- May be a natural inhibitor
- Melatonin levels are highest during childhood and decline in adulthood
- Removal of the pineal gland precipitates early puberty
8
Q
What are the 2 main functions of the Testes?
A
1) Spermatogenesis
2) Secrete Testosterone
9
Q
What is the primary location for the maturation and storage of sperm?
A
Epididymis
10
Q
What is the function of the Vas Deferens in regards to sperm and concentrating the sperm?
A
- Provides another storage area for sperm (ampulla)
- Secretes fluid rich in citrate and fructose (slightly acidic)
11
Q
What do the Seminal Vesicles secrete?
A
- Secrete fluid rich in: citrate, fructose, prostaglandins, and fibrinogen
- Adds considerable nutrient value for the ejaculated sperm
12
Q
What does the Prostate Gland secrete; when is it secreted?
A
- Milky aqueous solution rich in citrate, calcium, phosphate ion, a clotting enzyme, and a profibrinolysin
- Secreted during emission
13
Q
What makes up the Seminiferous Tubule?
A
Epithelium formed by the Sertoli cells, w/ interspersed germ cells
14
Q
What are spermatogonia vs. Spermatozoa; what are their location?
A
Spermatogonia: most immature germ cells, located near the periphery of the Seminiferous Tubule
Spermatozoa: mature germ cells, located near the lumen of the Seminferous Tubule
15
Q
Where are Leydig cells found and general function?
A
Interstitial cells that lie between the Seminiferous Tubules; synthesize and secrete testosterone
16
Q
What is the general function of Sertoli Cells?
A
- Provide nutrients to the differentiating sperm
- Form tight junction w/ each other, creating a barrier between testes and bloodstream
- Secrete an aqueous fluid into the lumen of the Seminferous Tubules, which helps transport sperm thru tubules into epididymis
17
Q
Which androgen are secreted by the testes; which is most abundant; and what occurs to the most abundant androgen in target tissues?
A
- Testosterone, dihydrotestosterone, and androstenedione
- Testosterone is the most abdundant
- In target tissues, much of the testosterone is converted into DHT by the enzyme 5α-reductase
18
Q
Why aren’t any glucocorticoids or mineralocorticoids synthesized in the testes
A
Lack 21β-hydroxylase and 11β-hydroxylase
19
Q
How are the testes able to get the end product of testosterone, unlike the adrenal gland?
A
- Have 17β-hydroxysteroid dehydrogenase, which converts androstenedione to testosterone
- End product of steroid synthesis in the testes is Testosterone, NOT DHEA and androstenedione like in the in the adrenal gland
20
Q
What occurs to testosterone in the lumen of the seminiferous tubules?
A
Is concentrated by binding to androgen-binding protein (ABP), which is synthesized by the Sertoli Cells
21
Q
In what tissues is DHT the active androgen; how do we get DHT from testosterone?
A
- Prostate gland in the adult and external genitalia of the male fetus, skin, liver
- Testosterone is converted by 5α-reductase, in peripheral tissue, to DHT
22
Q
Most of the circulating testosterone is bound to what?
A
- Plasma proteins: Sex hormone-binding globulin (SHBG)
- Albumin
23
Q
How are Leydig cells able to acquire the cholesterol necessary for steroidogenesis; how is this cholesterol stored?
A
- Can synthesize de novo
- Can acquire from circulation, through LDL receptors and HDL receptors
- Stored as cholesterol esters
24
Q
How is stored cholesterol within the testes able to be freed for use by the Leydig Cells?
A
Via HSL, which converts cholesterol esters to free cholesterol for androgen production
25
What happens to cholesteorl within the Leydig Cells of the testes after it is freed up via HSL?
- Transferred within mitochondrial membranes via the steroidogenic acute regulatory protein (**StAR**)
- Cholesterol is then converted to **pregnenolone** via **cholesterol desmolase**
26
Small amounts of estrogen are produced in males; where is the concentration highest in the reproductive tract and how is it produced (cell type and enzyme)?
- Fluid of the Seminferous tubules, the [estrogen] is high
- Comes from the **Sertoli Cells,** which produce **aromatase,** the enzyme that converts testosterone to estradiol
27
Why is estrogen produced in the male repro system and where else is it produced?
- Potential roles in **spermatogenesis**, since human sperm cells express at least one isoform of the **estrogen receptor (ER)**
- Much **larger amounts** of estrogens are formed from testosterone and androstenediol in other body tissues, with the **majority** being in the **liver**
28
What is the rate limiting step in the synthesis of testosterone in male repro system; mediated by what enzyme; where does it occur?
- In the **mitochondria**, by the **cytochrome P450 side-chain cleavage enzyme (P450SCC) aka Cholesterol Desmolase**
- Converts cholesterol to pregnenolone
29
What is the primary endocrine cells of the testes and what are its major and minor products?
- Leydig Cell producing Testosterone
- Makes limited amounts of DHT and estradiol-17β (majority is made via peripheral conversion)
30
Once Testosterone is made what are its 2 options?
1) Diffuses into seminiferous tubules and is concentrated by binding to **ABP**
2) Enter the peritubular capillary network and carried into peripheral circulation by **SHBG and albumin**
31
What is the importance LH in the production of testosterone from cholesterol?
- Stimulates the conversion of cholesterol to pregnenolone in Leydig Cells **(have LH receptor**)
- **Increases affinity** of P450scc enzyme for cholesterol
- Stimulates **synthesis of P450scc enzyme (long-term actio**n)
32
When does production of testosterone begin in fetus and where are androgen receptors found in repro. and non-repro tissue; are they found in the female?
- Around 7-8 weeks' gestation
- AR are found in: **prostate, testis (Sertoli, Leydig and myoid cells), epididymis, seminal vesicles**
- Non-repro tissues including: **neurons in CNS, anterior pituiatary, thyroid, skin, adrenal cortex, liver, kidney tubules, bladder, cardiac and striated muscle, bone, and vasculature**
- Also in female, in **ovary (interstitial and granulosa cells), mammary glands, uterus**
33
What type of receptor is the Androgen Receptor (AR)?
Nuclear Receptor; which directs protein synthesis
34
What binds the AR with greatest affinity and why is this important?
- DHT!
- Plays importat role in causing chanhes at puberty
- Deficiency of 5α-reductase results in ambigous external genitalia
35
What occurs as testosterone enters the peripheral circulation; how is it found?
- Quickly reaches equilibrium w/ serum proteins
- 60% is bound to **SHBG**
- 38% is bound to **albumin**
- 2% remains free, which is the biologically **active form**
36
How is testosterone and its metabolites disposed of by the body?
- Excreted **primarily** in the **urine**
- 50% of excreted androgens are found as **17-ketosteroids**
- Remainder being **conjugated** androgens or diol or triol derivatives
37
What is the androgen produced from cholesterol in adrenal vs. testis vs. peripheral tissues?
**Adrenal:** cholesterol ---\> androstenedione
**Testis**: cholesterol ---\> androstenedione --\> testosterone
- Some DHT and Estradiol produced
**Peripheral Tissues:** produce most of the DHT and estradiol from testosterone
38
What does testosterone cause during the last 2-3 months of pregnancy in a male; deficiency results in?
- Descent of testes into scrotum
- Cryptochidism = lack of descent
39
What 7 things is testosterone responsible for at puberty?
1) Increased muscle mass
2) Pubertal growth spurt
3) Closure of the epiphyseal plates
4) Growth of the penis and seminal vesicles
5) Spermatogenesis
6) Deepening of the voice
7) Libido
40
What are the specific actions of DHT in the fetus and throughout males life?
- Fetal differentiation of the external male genitalia (i.e., penis, scrotum, and prostate)
- Male hair distribution and male pattern baldness
- Sebaceous gland acitivity
- Growth of the prostate
41
What can be used as a treatment for benign prostatic hypertrophy and hair loss in males?
- 5α-reductase inhibitors
- Since these 2 things are dependent on DHT rather than testosterone
42
What are 4 androgenic actions in males?
1) Regulation of differentiation of male internal and external genitalia in fetus
2) Stimulation of growth, development of 2° sexual characteristics at puberty
3) Maintenance of reproductive tract and production of semen
4) Initiation and maintenance of spermatogensis
43
What are 7 Anabolic actions of androgens?
1) Stimulation of **erythropoietin** synthesis (RBC production)
2) Stimuation of sebaceous gland secretion
3) Control of protein anabolic effects (nitrogen retention)
4) Stimulation of **linear body growth**, bone growth, and closure of epiphyses
5) Stimulation of ABP synthesis
6) Maintenance of secretions of sex glands
7) Regulation of behavioral effects, including libido
44
What are the classic signs and symptoms of Benign prostatic hyperplasia (BPH)?
- Urinary frequency, urgency, nocturia (excessive urination at night)
- Difficulty intiating and maintaining urinary stream
- Feeling of postvoid fullness in bladder, and dribbling
45
What is thought to be the reason behind the effects of DHT on prostatic tissue in BPH?
- The concentrations of DHT are not higher
- May have **more DHT receptors on their prostates**
46
What type of pathway is initiated by LH binding its receptor on Leydig cells; stimulates what?
- cAMP-PKA pathway
- Results in: steroidogenesis and testosterone production
- Testosterone diffuses into seminiferous tubules and peripheral circulation
47
Sertoli cells are stimulated by what, via which pathway, causing what important things to be produced?
- Testosterone and FSH
- cAMP-PKA pathway
- **FSH** binding results in: protein synthesis and production of **inhibin** (inhibits FSH release), **ABP, aromatase, AMH**, and other products
48
What are the supportive functions of Sertoli Cells?
- Maintaining blood-testis barrier
- Phagocytosis
- Transfer of nutrients from blood to sperm (transferrin, Fe, lactate)
- Receptors for hormone and paracrines
49
What are the Exocrine functions of Sertoli cells?
- Production of fluid
- Production of ABP
- Determination of release of sperm from seminiferous tubule
50
What are the endocrine functions of Sertoli Cells?
- Expression of ABP, T and FSH receptors
- Production of AMH
- Aromatization of testosterone to estradiol-17β
- Production of inhibin to regulate FSH levels
51
Testosterone can cause negative feedback to, which decreases?
- Anterior Pituitary to **decrease LH**
- Hypothalamus (GnRH) to **decrease GnRH**
52
What is the function of inhibin; where does it come from?
- Produced by Sertoli Cells
- Negative feedback to Hypothalamus to **decrease GnRH** and to the Anterior pituitary to **decrease FSH**
53
The seminferous tubules are lined by a complex stratified epithelium containing two distinct cells, what are they?
1) Spermatogenic Cells that develop into Spermatozoa
2) Sertoli Cells which have a supportive and nutrient function
54
What are the 3 phases of Spermatogenesis?
1) Mitotic divisions
2) Meiotic divisions
3) Spermiogenesis
55
What does the mitotic divisions (spermatocytogenesis) produce?
- Proliferative phase
- At puberty, mitotic cycles increase and spermatogonia or stem cells divide to produce daughter spermatogonia
- After the last division, the resulting cells are called **1**° **spermatocytes (diploid 4N)**
56
What occurs during meiosis of the 1° spermatocytes?
- Undergo **two** meiotic divisions
- The **first** division produces **two 2**° **spermatocytes,** each w/ a **haploid number of duplicated chromosomes (2N)**
- 2° spermatocytes enter **second** meiotic division, producing two spermatids, each w/ a **haploid** number of **unduplicated chromosomes (1N)**
57
What is spermiogenesis; what occurs and where does it end?
- Spermatids undergo spermiogenesis, nuclear and cytoplasmic changes occur to produce mature spermatozoa
- Ends in testis w/ release of spermatozoa from **S****ertoli cells**
58
What are spermatogonium type A vs. type B?
Type A: remain as progenitor cells
Type B: go through the meiotic events
59
What occurs to the residual body produced during production of mature sperm?
Phagocytized by Sertoli Cells
60
What is the affect of LH on spermatogenesis?
- Secreted by Anterior Pituitary
- Stimulates the **Leydig cells** to secrete testosterone
61
What is the affect of FSH on spermatogenesis; what occurs with deficiency?
- Secreted by anterior pituitary
- Stimulates the **Sertoli cells** to nurse and form sperm
- Without this stimulation, spermatogenesis will **NOT** occur!
62
What is the affect of GH on spermatogenesis; what occurs with deficiency?
- Necessary for controlling background metabolic functions of the testes
- Promotes early division of the sperm themselves
- Without it, as seen in pituitary dwarfs, spermatogenesis is **severly deficient** or **absent** rendering them **infertile**
63
Why is testosterone essential for spermatogenesis?
Essential for **growth and division** of the testicular **germinal cells**, which is **beginning** of sperm formation
64
When is estrogen formed in male repro system and what may it be important for?
- Formed **from** the **testosterone** by the **Sertoli cells** when they are **stimulated** by **FSH**
- May be also essential for spermatogenesis
65
What occurs to the normal feedback loop in a man upon the administration of exogenous testosterone (or an androgenic analog)?
LH will be secreted at much lower levels than normal; since it is particularly sensitive to androgens
66
How motile are sperm entering the epididymis vs. leaving?
- Weakly motile upon entering
- Strong motile upon exiting
67
What decapacitation within the epididymis?
Addition of molecules to the membranes of sperm to **prevent** the **acrosomal reaction** before contact w/ an egg
68
What is the importance of prostaglandins found within the fluid secreted by seminal vesicles; how does it aid in fertilization?
- Reacts w/ the female cervical mucus to make it more receptive to sperm movement (**make cervical mucus less thick**)
- Causes **backward**, **reverse peristaltic contractions** in the uterus and fallopian tubes to move the ejaculated sperm toward the ovaries
69
What is the importance of the fluid secreted by the prostate gland?
- Causes **pH** adjustment
- Slightly **alkaline** prostatic fluid helps neutralize the acidity of the other seminal fluids during ejaculation and thus **enhances motility** and **fertility** of the sperm
70
What is the final pH of sperm?
7.5
71
What occurs once spermatozoa emerge from the efferent ductules?
They leave the gonad and enter the extratesticular portion of the reproductive tract (epididymis, vas deferns, ejaculatory duct, prostatic urethra, membranous urethra, and penile urethra)
72
What are the 2 main differences seen in a male repro. tract vs. female?
1) Continous lumen from the seminiferous tubule to the end of the male tract (i.e., the tip of the penile urethra)
2) Male tract connects to the distal urinary tract (i.e., male urethra)
73
What are the 3 erectile bodies of the penis?
- 2 corpora cavernosa
- 1 corpus spongiosum
74
What nerves control an erection; what molecule is released and what is the effect?
- Parasympathetic nerves innervating the vascular SM of the **helicine arteries** that supply blood to the **cavernous** spaces release **NO**
**- NO activates** **guanylyl cyclase, increases cGMP, which decreases intracellular Ca2+ and causes relaxation of the vascular SM**
75
What role does somatic stimulation play in an erection of the penis?
Increases contraction of muscles at the base of the penis further promoting erection
76
What nerves control the emission of sperm from the epididymis all the way to the ejaculatory ducts; what do they cause and what does this prevent?
- Sympathetic control (adrenergic transmitter)
- Causes **sequential peristaltic contraction of SM** of vas deferns, closing the **internal sphincter** of the **bladder**
- Preventing **retograde ejaculation** of the semen into the bladder
- Emission normally precedes ejaculation
77
What does destruction of the internal sphincter of the bladder by prostatectomy often lead to?
Retrograde ejaculation
78
The propulsion of semen out of the male urethra is caused by what muscles; innervated by what nerves?
- Rhythmic contraction of the **bulbospongiosus** and the **ischiocavernosus** muscles (**striated muscle**), surrounding base of the penis
- Innervated by **somatic motor nerves (Deep Perineal N.)**
79
What 3 changes lead to capacitation of sperm when they come in contact with the fluids of the female tract?
1) Uterine and Fallopian tubes wash away **inhibitory factors**
2) Loss of **cholesterol** that had built-up on the **acrosome,** which now make the head of the sperm **weaker**
3) Membrane of the sperm is much **more permeable** to **Ca2+; increases the motility of the sperm**
80
What is stored in large quantities in the acrosomal head of the sperm and how do they contribute to the acrosome reaction?
- **Hyaluronidase** depolymerized hyaluronic acid polymers in the intercellular cement that hold the ovarian granulosa cells together
- **Proteolytic enzymes** digest proteins in the structural elements of tissue cells that adhere to the ovum
81
What does testosterone deficiency lead to in the 2nd-3rd mo. of gestation?
Varying degres of ambiguity in the male genitalia and male pseudohermaphrodism
82
What does testosterone deficiency lead to in the 3rd trimester of pregnancy?
Problems in testicular descent (cryptorchidism) along w/ micropenis
83
What does testosterone deficiency lead to in puberty?
Poor secondary sexual development and overall **eunuchoid features**
84
What is Eunuchoidism?
Persistency of prepubertal characteristics and often by the presence of characteristics typical of the opposite sex
85
What does testosterone deficiency lead to Post-puberty?
Decreased libido, erectile dysfunction, decrease facial and body hair growth, low energy and infertility
86
How does Viagra work?
- 5 PDE inhibitor
- Stops Type 5 phosphodiesterase from converting cGMP --\> GMP
- Increased cGMP leads to an erection
87
What is Kallman's syndrome; characterized by what?
- GnRH neurons fail to migrate into the hypothalamus during embryonic development
- Characterized by delayed or absent puberty and an impaired sense of smell
- Form of hypogonadotropic hypogonadism
88
What is Klinefelter syndrome; phenotype; affect at puberty; androgen and gonadoptropin production?
- Seminferous tubular dysgenesis
- Male karyotype (46,XY) has **at least one extra X chromosome**
**-** Affected persons are **phenotypically** male because of the presence of Y chromosome; appear male at birth
- At puberty, **increased levels of gonadotropins (FSH, LH)** fail to induce normal testicular growth and spermatogenesis
- Androgen production is usually low (highly variable among patients), whereas the levels of gonadoptropins are **elevated**, thereby indicating **1**° **hypogonadism**
**- Seminiferous tubules** are **largely destroyed**, resulting in infertility
89
How is prostate cancer treated?
Androgen receptor antagonist, radiotherpay, radical prostatectomy
90
Tumors of the testis usually affect which cells and produce?
- Interstitial cells (Leydig Cells)
- Produce large amounts of testosterone
91
What hormones do germinal epithelial tumors produce?
NO hormones
92
What occurs to gonadal sensitivity to LH and androgen prodcution as men age; what affect does this have?
- Gonadal sensitivity to LH decreases and androgen prod. drops
- **Serum** LH and FSH levels **rise** (**FSH\>LH**)
- Testosterone decreases w/ age, slowly, causing decreased: **bone formation, muscle mass, growth of facial hair, appetite, and libido**
93
Inhibin and estradiol cause negative feed back where?
Anterior pituitary to **decrease FSH**
Hypothalamus to **decrease GnRH**
