W7L2 Intro + Male Reproductive Physiology Flashcards

1
Q

Gonadotropin-releasing hormone comes from ______ and goes to _____ to stimulate the release of ______ and _____

A

Gonadotropin-releasing hormone comes from the hypothalamus (arcuate nucleus) and goes the anterior pituitary (via portal circulation) to stimulate the release leutinizing hormone / lutropin (LH) and follicle-stimulating hormone (FSH)

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2
Q

What two ways do the gonads respond to activation by LH and FSH?

A
  1. Gametogenesis, 2. Produce hormones (which have neg feedback on hypothalamus and anterior pituitary)
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3
Q

What 4 types of hormones are produced by the gonads?

A
  1. Androgens (mostly testosterone),
  2. Estrogens (mostly Estradiol aka E2),
  3. Gestagens (mostly Progesterone aka P4),
  4. Inhibins
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4
Q

Testosterone can be converted into what important molecule that occurs almost exclusively in males and is associated with prostate function, increased facial hair, and baldness? What is the enzyme that converts it?

A

Testosterone -> DHT (dihydrotestosterone) via 5-alpha reductase

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5
Q

Testosterone can be converted into what important estrogen? Via what enzyme?

A

Testosterone -> Estradiol (E2) via CYP19

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6
Q

Androstenedione is converted into what estrogen?

With the above hormone as an intermediate, what other estrogen can be converted during pregnancy?

A

Estrone (E1), via aromatase

During pregnancy, DHEAS is produced by the fetal adrenal gland, which is then converted into estriol (E3) in the maternal placenta.

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7
Q

The mechanisms of action for sex hormones are classified as either ______, with a longer lag time, or ________, which has more rapid effects

A

Genomic (most important) or non-genomic mechanisms

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8
Q

What are two ways that estrogen can influence genomic changes in a cell?

A
  1. Estrogen binds to its receptor, goes to nucleus and binds special estrogen responsive elements, recruits other co-activators or co-regressors of transcription, and changes the transcription activity of pertinent gene.
  2. genes are waiting for estrogen to come, where the activators of gene expression are pre-assembled. Estrogen binds to complex, and turns off or on the transcriptional activity
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9
Q

What is an example of how transcription can be both induced and repressed by estrogen?

A

In hepatocytes, E2 increases synthesis of two coagulation factors (VIII and X), while decreasing synthesis of antithrombin III. Thus, high estradiol levels increase chance of thrombosis.

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10
Q

Leydig cells are affected by what hormone, and what do they produce?

Where does this provide negative feedback?

A

Influenced by LH to produce testosterone.

Testosterone reaches the arcuate nucleus, where it is converted to estrogen and performs neg feedback on GnRH production. Also performs neg feedback on anterior pituitary.

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11
Q

Sertoli cells are affected by what hormone, and what do they produce?

How does negative feedback occur with this?

A

Sertoli cells are influenced by FSH to take testosterone and use it to produce E2 and inhibin.

Inhibin provides negative feedback only on FSH production at the anterior pituitary.

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12
Q

If you give GnRH analogues that have a long-lasting effect, what will happen to LH and FSH production? Why?

A

Production will be shut-down because the receptors are quickly desensitized.

GnRH is typically produced in a pulsatile manner, and this is necessary to maintain proper sensitivity of GnRH receptors.

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13
Q

When are the two peaks of testosterone in early male development?

A

One during intrauterine development, then one right after birth. Testosterone doesn’t peak again until puberty

(may be a graph to draw)

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14
Q

At puberty, how do hormone levels change in males?

What changes occur when the male is older than 60?

A

At puberty, GnRH secretion increases, leading to FSH and LH increases, so a new steady state with high FSH/ LH occurs, leading to prolonged high testosterone levels.

After the age of 60, testosterone production declines, while FSH / LH secretion surprisingly increases.

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15
Q

What are gestagens (simply), and what is the main one?

A

Steroid hormones that support ongoing pregnancy.

The main one is progesterone, but it has a bunch of other roles besides this.

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16
Q

What type of crystals are visible in human Leydig cells?

A

Reinke crystals

17
Q

Why is it important that Leydig cells be in close contact with Sertoli cells?

A

Because testosterone is produced by Leydig cells and is then available in high concentrations to nearby locations.

If testosterone is given into the bloodstream from another location, it won’t be enough to work with sertoli cells and sperm undergoing maturation

18
Q

What type of GPCR does LH use to affect Leydig cells? And what GPCR for Sertoli cells via FSH?

A

Gs for both

19
Q

What is the effect on Leydig cells of estrogen that is produced by Sertoli cells?

A

Positive feedback that increases transcription of genes involved in testosterone production

Helps maintain constantly high level of testosterone for spermatogenesis

20
Q

For transport of androgens,
what percentage of testosterone is free?

70-80% is bound to what?

Nearly 20% is bound to what?

A

1-3% free

70-80% bound to Sex Hormone Binding Globulin-T (SHBG-T)

20% bound to CBG (cortisol binding) or Albumin

21
Q

How is testosterone produced in females?

A

Ovaries produce it, and infertile women still receive weak androgens (DHEA and androstenedione) via zona reticularis

22
Q

What is the effect on sex hormones during liver failure?

A

Because the liver takes up androgens for degradation and excretion, the steady state where produced amount and degraded/excreted amounts of hormones is disrupted.

So, steroids with estrogen effects accumulate more (estrogen dominance)

23
Q

What does pleiotropic effects mean? Androgens have pleiotropic effects.

A

Pleiotropic effects occur when one hormone (or could be referring to other things) create two or more seemingly unrelated effects.

24
Q

What are the endocrine effects of androgens?

A

Mostly negative feedback, inhibition of GnRH (by E2) and FSH/LH (by Testosterone or DHT)

25
Q

What are the effects of androgens on sexual development and differentiation?

(Broadly, because this will be covered more in the next lecture)

A

intrauterine, perinatal and pubertal sexual differentiation (T / DHT)

26
Q

What are the effects of androgens on the male sex organs?

A

Normal spermatogenesis and genital gland function (T/ DHT)

27
Q

What are the effects of androgens on the CNS?

A

Increases sex drive, aggression, competitive behavior, general “male-like” behavior but affects both sexes

(testosterone)

28
Q

What are the effects of androgens on skin and body hair?

A

Sebaceous gland secretions increased (causing acne), baldness, male-associated facial hair

(DHT)

29
Q

What are the effects of androgens on muscle and bone?

A

Anabolic effects, causing skeletal muscle growth and mass maintenance, plus bone mass increase, osteoblast activation, and increased mineralization of bones (partly also from E2)

30
Q

What are the effects of androgens on bone growth during puberty?

A

Favors longitudinal growth. However, if present in high concentrations, it induces closure of epiphyseal plate (via E2)

So first it favors growth, but then high concentrations shut growth down.

31
Q

What is the effect of androgens on red blood cells and cholesterol?

A

Transcription of hemoglobin increases (higher hematocrit in males usually)

LDL / HDL ratio is higher, leading to increased cardiovascular disease

32
Q

What type of obesity is more common in males in relation to androgen levels?

A

Visceral obesity, which increases type 2 diabetes mellitus risk and metabolic syndrome.

33
Q

What is the difference between spermatogenesis and spermiogenesis?

A

Spermatogenesis covers the whole process of mitosis and meiosis leading to mature spermatozoa.

Spermiogenesis refers to the maturation of just spermatids into sperm cells (later steps)

34
Q

What are the 6 steps of spermatogenesis up until spermatids are formed?

(recommend to be able to draw it)

A
  1. Parent cell (spermatogonium, primary spermatocyte) has 2 chromosomes, diploid cell
  2. Chromosomes make identical copies of themselves
  3. Similar chromosomes pair up (homologous pairs)
  4. Crossing over occurs, get new combination of genes
  5. Pairs of chromosomes divide, and form secondary spermatocytes
  6. Chromosomes divide, forming immature spermatids that contain only 1 copy of each chromosome
35
Q

What is the way that males overcome the fact that the immune system would recognize and attack maturing sperm cells because they were not produced until puberty began?

A

An “immunologically-privileged site” is formed, resulting from the tight junctions between Sertoli cells that prevent immune cells from entering the places where sperm cells are located

36
Q

LH and FSH have what effect on the seminiferous tubules?

A

Before puberty, males have small seminiferous tubules. When LH and FSH begin to be secreted at puberty, they make the tubules develop to be larger/thicker, plus contain all the necessary cells for sperm maturation

37
Q

What vitamins are necessary for sperm production?

A

A, B, E, D

“a bed”

38
Q

Around what temperature should the testis be for sperm production?

A

30-32 degrees C. This is the reason why testis descend outside the abdominal cavity.

39
Q

What molecule is necessary for cell-to-cell interactions in maturing sperm?

A

ICAMs: intracellular adhesion molecules. Reside in the Sertoli cell membranes and are used to stick to the maturing sperm cells