W7L2 Intro + Male Reproductive Physiology Flashcards
(39 cards)
Gonadotropin-releasing hormone comes from ______ and goes to _____ to stimulate the release of ______ and _____
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)
What two ways do the gonads respond to activation by LH and FSH?
- Gametogenesis, 2. Produce hormones (which have neg feedback on hypothalamus and anterior pituitary)
What 4 types of hormones are produced by the gonads?
- Androgens (mostly testosterone),
- Estrogens (mostly Estradiol aka E2),
- Gestagens (mostly Progesterone aka P4),
- Inhibins
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?
Testosterone -> DHT (dihydrotestosterone) via 5-alpha reductase
Testosterone can be converted into what important estrogen? Via what enzyme?
Testosterone -> Estradiol (E2) via CYP19
Androstenedione is converted into what estrogen?
With the above hormone as an intermediate, what other estrogen can be converted during pregnancy?
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.
The mechanisms of action for sex hormones are classified as either ______, with a longer lag time, or ________, which has more rapid effects
Genomic (most important) or non-genomic mechanisms
What are two ways that estrogen can influence genomic changes in a cell?
- 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.
- 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
What is an example of how transcription can be both induced and repressed by estrogen?
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.
Leydig cells are affected by what hormone, and what do they produce?
Where does this provide negative feedback?
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.
Sertoli cells are affected by what hormone, and what do they produce?
How does negative feedback occur with this?
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.
If you give GnRH analogues that have a long-lasting effect, what will happen to LH and FSH production? Why?
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.
When are the two peaks of testosterone in early male development?
One during intrauterine development, then one right after birth. Testosterone doesn’t peak again until puberty
(may be a graph to draw)
At puberty, how do hormone levels change in males?
What changes occur when the male is older than 60?
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.
What are gestagens (simply), and what is the main one?
Steroid hormones that support ongoing pregnancy.
The main one is progesterone, but it has a bunch of other roles besides this.
What type of crystals are visible in human Leydig cells?
Reinke crystals
Why is it important that Leydig cells be in close contact with Sertoli cells?
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
What type of GPCR does LH use to affect Leydig cells? And what GPCR for Sertoli cells via FSH?
Gs for both
What is the effect on Leydig cells of estrogen that is produced by Sertoli cells?
Positive feedback that increases transcription of genes involved in testosterone production
Helps maintain constantly high level of testosterone for spermatogenesis
For transport of androgens,
what percentage of testosterone is free?
70-80% is bound to what?
Nearly 20% is bound to what?
1-3% free
70-80% bound to Sex Hormone Binding Globulin-T (SHBG-T)
20% bound to CBG (cortisol binding) or Albumin
How is testosterone produced in females?
Ovaries produce it, and infertile women still receive weak androgens (DHEA and androstenedione) via zona reticularis
What is the effect on sex hormones during liver failure?
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)
What does pleiotropic effects mean? Androgens have pleiotropic effects.
Pleiotropic effects occur when one hormone (or could be referring to other things) create two or more seemingly unrelated effects.
What are the endocrine effects of androgens?
Mostly negative feedback, inhibition of GnRH (by E2) and FSH/LH (by Testosterone or DHT)
