Endocrinology/Objectives/Lecture 6
From PhysioWiki
Endocrinology of the testis and the male reproductive tract
LIST the cell types of the testes; INDICATE their function.
| Cell type | Function |
|---|---|
| Leydig cells | Synthesize testosterone in response to LH |
| Sertoli cells | Spermatogenesis, inhibin synthesis in response to FSH |
DRAW a diagram showing the interrelationship between the hypothalamus, anterior pituitary, and testes (stimulatory and inhibitory effects.
(See figure.)
DESCRIBE the secretion, transport, and metabolism of testosterone.
Synthesis
LH binds -> G protein -> adenylyl cyclase -> cAMP -> PKA -> cholesterol -> testosterone.
Secretion
Testosterone is synthesized and secreted in response to LH from the anterior pituitary. Because it is a steroid and therefore lipid-soluble, it leaves the Leydig cells by simple diffusion. Its classical actions are via an endocrine (blood-borne) system. Testosterone also acts in a paracrine (locally, not through blood) on adjacent Sertoli cells to promote spermatogenesis. Like many other hormones, testosterone secretions are pulsatile and vary with GnRH and LH levels.
Transport
After secretion, testosterone is transported through blood in both free and bound states. Only free (ie, unbound) testosterone is biologically active (eg, only free testosterone can exert negative feedback). Bound testosterone is carried by a number of testosterone-binding proteins, including sex steroid binding protein and albumin.
Metabolism
Depending on the target tissue, testosterone may affect the transcriptional apparatus directly as testosterone or after convertion to DHT by 5alpha-reductase. It may also be converted to estrogen by aromatase.
LIST the physiologic actions of testosterone.
| Hormone | Fetal development | Pubertal development | Adult effects |
|---|---|---|---|
| Testosterone |
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| Dihydrotestosterone |
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DESCRIBE the body changes at puberty in boys (male secondary sex characteristics).
During puberty, androgens (principally testosterone and DHT) promote the development of the structures listed above.
PREDICT the effect of castration on prepubertal and mature individuals.
Prepubertal castration results in impaired development of the penis, scrotum, prostate, skeleton, musculature, larynx, pubic hair, sebaceous glands, lack of spermatogenesis, libido. The individual would be less aggressive and possibly depressed (because of testosterone's influence on a feeling of well being).
Postpubertal castration would result in reduction in secondary sex characteristics, loss of axial and pubic hair (though reduced loss of crown hair due to lack of DHT), reduced musculature, reduced libido, and other structures maintained by androgens. Reduced aggression and depression may also result as discussed above.
He would also be pissed because you removed his testicles.
DESCRIBE the function of inhibin; where is it synthesized?
Inhibin is synthesized and secreted by Sertoli cells. It exerts long-loop negative feedback on FSH secretion in the anterior pituitary.
It is a heterodimer of alpha and beta subunits; there is only one alpha subtype, whereas there are two beta subtypes (beta-A and beta-B). Alpha,beta-A produced inhibin A, and alpha,beta-B produces inhibin B.
They are structurally related to activins, which are composed of two beta subunits. There are three types of activin, A (beta-A,beta-A), B (beta-B,beta-B), and AB (beta-A,beta-B). Activins are secreted in physiologically insignificant levels from the testes; most is secreted by FSH-producing cells of the anterior pituitary and participates in the regulation of FSH secretion.
DESCRIBE disease states associated with defective hypothalamic, pituitary, and testicular function.
Hypogonadotropic hypogonadism results from a lack of GnRH secretion. This may be a consequence of failure of GnRH-secreting neurons to migrate during embryogenesis from olfactory epithelium to the medial preoptic and arcuate nuclei of the hypothalamus. The result is a lack of GnRH, which results in a lack of LH and FSH, leading to lack of testosterone and a failure of secondary sexual development (which also includes a sense of well-being, confidence, etc.). Because Mullerian inhibiting factor is present, female internal reproductive structures are absent. Affected individuals are phenotypically male, but underdeveloped. Treatment is with testosterone replacement.
Precocious puberty may result from a pituitary adenoma (resulting in oversecretion of GnRH) or trauma. The result is that the onset of puberty is several years ahead of the normal age of onset. Since this can have social and physiological consequences (eg, premature closure of the epiphyseal plate), treatment is necessary and can be accomplished with administration of a GnRH agonist at high levels. Constant GnRH administration suppresses the pulsatile GnRH levels, and since GnRH pulsatility is a stimulus for LH and FSH release, LH and FSH levels fall rapidly. GnRH agonist administration can be withdrawn when it is appropriate to induce puberty.
Androgen resistance (known previously as testicular feminization) results from a functional loss of androgen receptors in a genetic (XY) male. The disease results in:
- Failure of testicular descent (as descent is in response to testosterone)
- Lack of spermatogenesis (requires testosterone as well as cool environment away from the abdomen)
- No female structures (as genetic males, affected individuals have AMF, which obliterates female internal reproductive structures)
- No virilization, resulting in superficially female phenotype
- Amenorrhea (no uterus, ovaries, or vagina; only blind-ending vaginal pouch)
- Infertile
- Increased body fat
- Elevated estrogens (from adrenal, gonads, and fat tissue)
- Positive feedback: increased fat tissue increased amount of aromatase activity, resulting in more testosterone->estrogen conversion
DESCRIBE the hormonal changes of puberty.
At the onset of puberty, elevated LH and FSH result in a rise in testosterone and in spermatogenesis, respectively. Many developmental effects are mediated by testosterone through its conversion to DHT or estradiol.
