Phys

Question 1

What is the principal hormonal regulator of Leydig cells, and what are the major functions of these cells?

Answer 1

Regulated by LH

Production of testosterone and Inhibin B in

Question 2

What is the principal hormonal regulator of Steroli cells, and what are the major functions of these cells?

Answer 2

Regulated by FSH

Forms Sertoli Barrier

In embryonic development: produces inhibin and anti-mullerian hormone

In puberty/adulthood: produces ABG and enzymes

Question 3

What enzyme converts T into DHT?

Answer 3

5-a-reductase

Question 4

What negative feedback function does testosterone have?

Answer 4

Travels to hypothalamus and provides (-) feedback inhibiting GnRH release (reducing production of both LH and FSH)

Question 5

What negative feedback function does inhibin have?

Answer 5

(Inhibin B: produced by Sertoli cells in response to FSH stimulation)

Travels to hypothalamus and inhibits production of FSH

Question 6

What relationship exists between GnRH and male fertility?

Answer 6

GnRH is released in a pulsatile fashion (GnRH –> FSH –> LH). If this pathway is continuously stimulated, infertility is likely to occur due to down-regulation of GnRH receptors in the anterior pituitary (down-regulated due to saturation with GnRH). This inhibits testosterone production, which negatively impacts fertility.

Question 7

Kisspeptin has what role in GnRH signaling?

Answer 7

Kisspeptin is released from KISS-1 cells when stimulated by leptin (released from adipocytes). This begins the pulsatile release of GnRH at the start of puberty.

Question 8

What physiologic adaptation occurs in hypothalamic/pituitary receptors during puberty?

Answer 8

Receptors in the HPA are less sensitive to androgens during puberty.

This allows testosterone to build up in the system (while avoiding down-regulation of receptors).

Question 9

Generally describe the production of testosterone, estrogen, inhibin B, and ABP.

Answer 9

Synthesis of all of these occur in the Leydig and Sertoli cells. LH or FSH bind a Gs receptor –> andenylyl cyclase –> cAMP –> PKA to stimulate protein synthesis.

Leydig cells produce testosterone during this process.
Sertoli cells produce Inhibin, ABP, and aromtase via this process.

Aromatase is responsible for the conversion of T –> E2.

Question 10

What occurs in 17-B-HSD deficiency?

Answer 10

17-B-HSD is responsible for the conversion of androstendione –> testosterone

In 17-B-HSD deficiency, androstendione accumulates and T is deficient. Because androstendione is a weak androgen, sexual development is impaired.

Question 11

Generally describe the pathway responsible for testosterone synthesis

Answer 11

LH binds recepton of Leydig cells, allowing entry of cholesterol

Cholesterol –> pregnenolone –> androstendione –> (Via 17-B-HSD) –> testosterone

Question 12

Generally describe the pathway responsible for estrogen synthesis

Answer 12

LH binds recepton of Leydig cells, allowing entry of cholesterol

Cholesterol –> pregnenolone –> androstendione –> (Via 17-B-HSD) –> testosterone

Testosterone travels to Sertoli cells, where aromatase converts T –> E2

Question 13

Generally describe the pathway responsible for DHT synthesis

Answer 13

LH binds recepton of Leydig cells, allowing entry of cholesterol

Cholesterol –> pregnenolone –> androstendione –> (Via 17-B-HSD) –> testosterone

Testosterone travels to peripheral and Sertoli cells, where 5a-reductase convert T –> DHT

Question 14

What is responsible for the surge of testosterone during male fetal development?

Answer 14

Fetal hCG

Question 15

What is responsible for the surge of T that drives spermatognoia in the male neonate?

Answer 15

LH

Question 16

At what time should [T] levels ideally be taken?

Answer 16

~8-10 AM, when they are highest

Question 17

When reading a testosterone measurement, what is being reported? What is a normal level?

Answer 17

300 - 950 WNL

~50% of that is SHBG bound (not bioavailable)

~ 40-50% is albumin-bound (bioavailable)

~ 1-2% is free (bioavailable, acts as negative feedback)

Question 18

Compare and contrast SHBG and ABG

Answer 18

Both bind testosterone

• SHBG binds T that is in the plasma
• ABG binds T in the Sertoil cells, allowing it to accumulate and be used for local spermatogenesis

Question 19

Name 2 physiological processes that require T, DHT, and E2 (all three hormones required)

Answer 19

• Imprint of male-pattern gonadotropins, sex drive, and behavior
• Sperm production

Question 20

What hormones can provide negative feedback to the HPA, inhibiting GnRH release?

Answer 20

T
DHT
E2

Question 21

Describe how testosterone signals as a steroid

Answer 21

• SHBG-bound T (or DHT) travels to androgen-receptive cells
• Diffuses into cell
• 5a-reductase converts T into DHT (if applicable)
• DHT binds androgen receptor protein (has attached HSP which stabilizes protein)
• Binding triggers dimerization, hyperphosphorylation, and nuclear translocation
• Once in nucleus, acts as transcription factor for downstream genes

Question 22

Describe the process of maturation from germ cell to spermatozoon

Answer 22

• At birth, germ cells w/46 single chromosomes are present –> convert to spermatogonium
• Spermatogonium stay inactive ~12 years
• T, DHT, and GH trigger mitosis: spermatogonium –> primary spermatocyte with 46 sister chromatids
• Meiosis I occurs: 2 haploid secondary spermatocytes each with 23 sister chromatids)
• Meiosis II occurs: each haploid spermatocyte –> 2 haploid spermatids each with 23 single chromosomes
• Spermiogenesis matures the spermatids into spermatozoon (requires FSH to produce aromatase allowing T –> E2)

Takes ~74 days so this must be a continuous process

Question 23

An individual with pituitary dwarfism may experience infertility due to interruption of what stage of sperm maturation?

Answer 23

GH is needed for mitosis of spermatogonium –> primary spermatocyte

Question 24

What changes must sperm cells undergo in order to achieve fertilization?

Answer 24

Capacitation and acrosome reaction; increases motility of sperm and allows them to penetrate hyaluronic acid-rich zona pellucida and fuse/penetrate egg

Question 25

Describe the process of capitation.

Answer 25

Capacitation allows sperm to become “better swimmers”: fluid from uterus and oviducts wash inhibitory factors from sperm –> loss of cholesterol in head –> increased permeability –> influx of Ca2+ allows better motility

Question 26

Describe the acrosome reaction.

Answer 26

As sperm reaches zona pellucida, the high concentration of hyaluronic acid triggers the acrosome membrane to fuse with plasma membrane of the sperm’s head. As this occurs, the head becomes “leaky” and secretes a hyaluronidase enzyme, allowing the sperm to move through the zona pellucida.

Question 27

What are the cell types involved in the parasympathetic-driven stage of the male sexual act, and what are their functions?

Answer 27

The erection stage is parasympathetic NS-mediated.

Cell types:
Non-adrenergic neurons: release NO

Endothelial cells: Synthesize NO

Smooth muscle cells: NO activates guanylate cyclase (GTP –> cGMP) –> PKG; causes smooth muscle relaxation

Adrenergic cells: Release PGE1; activates adenylate cyclase (AMP –> cAMP) –> PKA; causes smooth muscle relaxation

Question 28

What occurs during the emission phase of the male sexual act, and under what command are those actions?

Answer 28

Emission = sympathetic command

Ejaculate moves into the urethral bulb via contractions of the vas deferens and seminal vesicles. These contractions are caused by the binding of catecholamines to a-adrenergic receptors.

Question 29

What occurs during the phase of the male sexual act that is driven by both the sympathetic and somatic nervous systems?

Answer 29

The ejaculatory phase is under sympathetic and somatic command.

Involuntary spinal reflexes cause contraction of the ischiocavernosus and bulbocavernosus muscles, and increased peristaltic contractions of the prostate, seminal vesicles, and vas deferens occurs.

Question 30

What systems command the resolution phase of the male sexual act?

Answer 30

SNS, mediated by endothelin and PGF2a

Endothelial cells release endothelins and PGF2a; both stimulate a GPCR –> IP3/DAG second messenger system –> increase in Ca2+ influx causes smooth muscle contraction and constriction of vasculature.

The SNS contributes to this phase via NE binding a1 and a2 receptors. a1 causes smooth muscle contraction similarly to above; a2 inhibits adenylyl cyclase reducing cAMP, allowing Ca2+ entry into cell

Question 31

Give a general description of the four stages of the male sexual act and name the regulating systems for each.

Answer 31

1.) Erection and lubrication – Parasympathetic control.
Engorgement of the cavernous spaces and release of glandular fluids occurs.

2.) Emission – Sympathetic control.
Sperm, prostatic fluid and seminal fluid move into the internal urethra.

3.) Ejaculation – Sympathetic and Somatic control.
The SNS continues emissions (without which ejaculation is not possible); the somatic nervous system increases pressures via rhythmical contractions to propel ejaculate.

Question 32

Compare and contrast Klinefelter’s and Kallman’s Syndromes.

Answer 32

Both are forms of hypogonadism in which testosterone secretion is decreased.

Klinefelter’s is primary hypogonadism, and occurs in XXY individuals. The testicles do not respond to signals from the anterior pituitary, causing T to drop and LH to rise.

Kallman’s is a form of secondary hypogonadism, where inadequate GnRH causes delayed or absent puberty and subsequent low testosterone.

S/S are similar; Kallman’s has characteristic loss of smell.

Question 33

What contributions to bladder function does the sympathetic nervous system make?

Answer 33

At rest, sympathetic tone causes relaxed detrusor muscle and contracted internal urethral sphincter via the hypogastric nerve.

Question 34

What contributions to bladder function does the somatic nervous system make?

Answer 34

At rest, somatic tone causes a contracted external urethral sphincter via the pudendal nerve.

During micturition, the somatic nervous system allows voluntary relaxation of the external urethral system via the pudendal nerve.

Question 35

What contributions to bladder function does the parasympathetic nervous system make?

Answer 35

During micturition, the PNS causes a contraction of the detrusor muscle and relaxation of the internal urethral sphincter via the pelvic nerve.