Why is the temperature of the testes lower than the body?
It is required for sperm and hormone production
Where does spermatogenesis occur?
Inside semifierous tubules, and then sperm matures inside the epididymus (where it is held up to 18-24hrs and gains flagella) before going to the vas deferens where it is stored in the suppressed state up to 1 month
When does spermatogenesis occur in life?
Starts at puberty and continues throughout life
T or F. Sertoli cells are temp sensitive
T. Increased temp= decreased sperm productiona and decreased inhibin (increased temp is associated with varicocele and cryptorchidism)
Intersitial Leydig cells are responsible for what? These are located outside of the seminiferous tubules
Testosterone production when stimulated by LH from the pituitary (testosterone then feedback inhibits both LH and GnRH release)
NOTE: Testosterone production is not affected by temperature changes
Functions of Sertoli cells (these are primarily stimulated by FSH)?
-provide factors needed for the development and protection of sperm
-forms the blood-testis barrier
-produce sex hormone binding globulin (testosterone transporter)
-inhibin production (neg. feedback on FSH in anterior pituitary)
-produce growth factors to activate Leydig cells and promote testosterone production
-elimination of defective sperm via phagocytosis
-secrete AMH to cause regression of the female mullerian ducts
-estradiol production from testosterone via aromatase
Androgens are mainly (95%) made in _____ cells in males
How is testosterone made?
In the leydig cells:
1) cholesterol is converted to pregnenolone via CYP11A1
2) Pregnenlone is converted to 17-hydroxypregnenolone via 17a-hydroxylase
3) 17-hydroxypregnenolone is converted to DHEA (the first androgen) via 17,20-lyase
4) DHEA is converted to andreostenedione via 3B-HSD
5) Androstenedione is converted to testosterone via 17B-HSD
What happens to testosterone?
It is the major hormone secreted by the testes (4-10 MG/DAY) or it can be converted to estradiol because the sertoli cells express some aromatase (note that both testosterone and androstenedione can be converted to estrogen in adipose tissue as well)
At target cells, testosterone is converted to DHT via 5a-reductase
Is testosterone made during gestation?
Yes, it begins at 8 weeks and peaks at 12-18 weeks of gestation via leydig cell production and is responsible for differentiation of the fetal genitourinary tract, gender formation, and masculinization of the external genitalia (among other things)
Outline testosterone levels during life
The level of testosterone is somewhat high before birth and drops at birth until a transient minipuberty at 2-3 mo. of age (needed for brain development). Then a large rise is seen at puberty (10-15yo) and the max. level is maintained from 20-50 yo with some subsequent decrease after age 50 (but not as much drop as in women) (aka andropause)
Describe the production of male sex hormones via the hypothalamic axis
GnRH promotes secretion of FSH and LH from the anterior pituitary. FSH acts on sertoli cells to stimulate/nurture spermatogenesis and LH acts on leydig cells to stimulate testosterone production. Testosterone then helps stimulates sperm production via Sertoli cell stimulation, promotes secondary sex characteristics in males, and negatively feedbacks on the LH production (among other things)
What provides negative feedback on FSH?
Inhibin from sertoli cells
How does testosterone circulate?
What binds testosterone?
High affinity specific binding: Beta globuline like SSBG and
low affinity binding: Albumin
What mediates the long term effects of testosterone?
Androgen-responsive cells increase protein synthesis after testosterone diffuses through the cell and is converted to DHT via 5a-reductase which then binds to cytoplasmic receptor proteins which translocate to the nucleus
What mediates the non-genomic effects (immediate) effects of testosterone?
receptor-mediated responses via T and DHT binding, both on the membrane and in the cytosol, work via secondary messenger cascades
What are the effects of T AND DHT in the male?
1) Stimulate spermatogenesis by Sertoli cells
2) Maintain the function of the male genital tract (Seminal vesicles-T; prostate- DHT)
3) Induce male secondary sex characteristics
4) Stimulate protein synthesis
5) Required for sex drive and aggressive behavior
6) T feedback on GnRH and LH
As mentioned, estrogen is also made in men. Where is the bulk of estrogen produced (from testosterone) in men? How?
80% in the liver, and the rest in the testes, muscle, brain, and fat cells via aromatase
NOTE: The levels of estrogen in males is about 1/5 that of women
Why do men make estrogen?
It is needed for male fertility during reproductive age (present in seminiferous tubules and controls spermatogenesis)
Production of estrogen in males increases with what?
age and obesity
What are some exogenous sources of estrogen that can lead to estrogen overdose in men?
-foods (milk, meat, and eggs)
What are some potential symptoms of estrogen overdose in men?
BPH or cancer
low sex drive or impotence
heart disease, stroke, weight gain
What are some things just mediated by testosterone in men?
-muscle growth and enhanced sex drive
-differentiation of epididymis, vas deferens, and seminal vesicles (internal!)
-deepening of voice
-spermatogenesis, RBC production
-penis and seminal vesicle growth
-puberty growth spurt and cessation (epiphyseal closure) via estrogen converted from testosterone
-neg feedback on LH
What are some things just mediated by DHT in men?
-hair growth (pubic, chest and facial hair) and baldness
-increasing thickness and secretion of sebaceous glands
-differentiation of penis, prostate, and scrotum (external!)
What are some things mediated by DHT AND testosterone in men?
-development of male secondary sex characteristics
-bone growth and Ca retention
-increased eryhtropoietin synthesis
-fight depression and enhance aggressive behavior
-decrease body fat
What are the clinical uses of anabolic steroids?
hormone replacement therapy
-delayed puberty tx
-diseases that result in loss of lean muscle mass (cancer, AIDS, etc.)
What are some complications of androgen abuse?
-reduced spermatogenesis, testicular atrophy via suppression of the HPG axis
-breast enlargement in men (when testosterone is converted to estradiol via aromatase due to high exogenous levels)
-masculinization in women
-liver and kidney disease, including cancer
-high BP and MI
-aggression, mood swings, anxiety, etc.
What are the effects of 5a-reducstase deficiency?
SRY would still be present so genetics= XY
Internal: testes and internal organs would differentiate; no uterus, fallopian tubes (AMH still produced)
External: vagina/ambiguous b/c DHT mediates this! Might see more male external development at puberty (Guevedoces or penis at 12)
Hormones: Normal or high LH
Does having high levels of cholesterol (LDL) in the body lead to high levels of sex hormones?
Testosterone has no correlation with cholesterol levels, while high-cholesterol groups show lower E2 (estradiol) levels
NOTE: Statins have no effect on testosterone or estrogen levels