Lecture 18- Male Reproductive Endocrinology Flashcards
Hormonal control of the male reproductive system
Endocrine secretions from the hypothalamus, anterior pituitary + gonads= control the male reproductive system
*GnRH= controls secretion of gonadotrophins by the anterior pituitary
*FSH= responsible for the integrity of the seminiferous tubules + after puberty is important in gametogenesis through an action on Sertoli cells which nourish and support developing spermatozoa
*LH= (interstitial cell-stimulating hormone ICSH)- in male= stimulates the interstitial cells to secrete androgens (testosterone)
^secretion begins at puberty + consequent secretion of testosterone causes maturation of reproductive organs + development of secondary sexual characteristics
Hormonal control of the male reproductive system
After puberty, primary function of testosterone= maintenance of spermatogenesis in the Sertoli cells-fertility action
- testosterone = important in the maturation of spermatozoa as they pass through the epididymis and vascular deferens
- has marked anabolic effects = development of the musculature + increased bone growth -> rapid increase in height (pubertal growth spurt) + the closure of the epiphyses of long bones
- secretion= usually controlled by LH
Androgens
Testosterone
5a-dihydrotestosterone (DHT)
Androstenedione
Dehydroepiandosterone (DHEA)
- group of steroids that have anabolic + masculinising effects in both males and females
- testosterone= most important androgen in humans
Synthesised in;
- leydig cells of the testes = in males
- ovaries in females= small amounts
- adrenal gland = both sexes
Pharmacological actions of androgens
Effects of exogenous androgens = same as those of testosterone + depend on the age and sex of recipient
Boys at the age of puberty;
- rapid development of secondary sexual characteristics
- maturation of the reproductive organs + a marked increase in muscular strength
- height increases more gradually
- anabolic effects can be accompanied by retention of salt + water
- skin thickens + may darken and sebaceous glands become more active = can result in acne
- growth of hair on the face, pubic + axillary regions
- vocal cords hypertrophy = lower pitch to voice
- androgens = feeling of well-being and increase in physical vigour + may increase libido
Pharmacological actions of androgens
Pre-pubertal males;
- individuals concerned- don’t reach predicted height because of premature closure of the epiphyses of the long bones
Women;
-administration of ‘male’ doses to women= masculinisation but lower doses - restore plasma testosterone to normal female concentrations + improve sexual dysfunction in women following ovariectomy without adverse effects
Therapeutic uses of androgens
Replacement therapy due to inadequate androgen secretion;
- hypogonadism = due to testicular dysfunction (primary hypogonadism)
- hypogonadism due to failure of the hypothalamus or pituitary (secondary hypogonadism)
*Senile osteoporosis + chronic wasting= associated with human immunodeficiency virus/cancer
- adjunct therapy in severe burns and to speed recovery from surgery/chronic debilitating diseases
Adverse effects of androgens
Masculinisation in women-acne, growth of facial hair, deepening of voice, male pattern baldness + excessive muscle development
Males= excess androgens cause priapism
impotence -> decreased spermatogenesis
Androgens= stimulate prostrate growth
Androgens= increase serum LDL and lower serum HDL levels; risk of premature CHD
^high doses in young athletes= reduction of testicular size and increased aggression
Children= androgens can cause abnormal sexual maturation + growth disturbances resulting from premature closing of the epiphysis of the long bones
Testosterone
Principal androgen secreted by the mature testis
Aging= no sharp drop in testosterone (unlike oestrogen in postmenopausal women)
Blood- 98% of testosterone binds to binding proteins; albumin and androgen binding protein in Sertoli cells
Other 2% of testosterone can diffuse out the blood
Liver= main organ for breakdown of testosterone= can convert to other steroids
Anti-androgens
Used in treatment of patients producing excessive amounts of testosterone; e.g. prostatic cancer (PC)
*Cyproterone= partial agonist at androgen receptors- competing with dihydrotestosterone for receptors in androgen-sensitive target tissues; used as part of treatment of PC
*Finasteride= inhibits the enzyme (5a-reductase)= converts testosterone to dihydrotestosterone - used in benign prostatic hypertrophy (enlarged prostate)
*Flutamide- acts as competitive inhibitor of androgens at target cells - used in treatment of PC
*Ketoconazole= used primary in the treatment of fungal disease, is an inhibitor of adrenal + gonadal steroid synthesis
Causes of male infertility
-Hypogonadism; low levels of testosterone
-Drugs;
- sulfasalazine = anti-inflammatory drug for rheumatoid arthritis
- long term use of anabolic steroids
- chemo
