Androgens - Effects of testosterone and dihydrotestosterone
Testosterone and dihydrotestosterone act at the nuclear level by modulating protein synthesis. They act on the same receptor but dihydrotestosterone has more affinity for the receptor than testosterone. Schematically, dihydrotestosterone is the active hormone at the sexual level, while testosterone appears active as an anabolic and inhibitor of the secretion of the pituitary stimulins.
Estradiol, in men, as shown in men with a complete aromatase defect, has a certain number of effects, for example it contributes to epiphyseal fusion.
Sexual effects
- During the sexual differentiation of the embryo:
The presence of a normal Y chromosome (chromosomal sex) determines the differentiation of the bipotential embryonic gonad into the testis. The secretion of testosterone by the fetal testes (gonadal sex) which begins about the eighth week after conception, determines the male phenotype. In the absence of gonads, ovaries or testes, differentiation occurs towards the female phenotype. Under the influence of testosterone and its active metabolite, dihydrotestosterone, there is a development of wolffian ducts forming the epididymis, vas deferens, seminal vesicles, prostate and regression of müllerian ducts, probably by proteolytic enzyme activation. The anti-mullerian hormone, a dimeric glycoprotein secreted by the fetal testes, inhibits the development of müllerian ducts and elicits their involution. Another protein, called SF-1 (steroidogenic Factor-1), secreted by testicular Sertoli cells, is implicated in sexual differentiation.
In the female fetus, in the absence of testosterone, there are persistence and development of müllerian ducts and absence of the development of wolffian ducts.
This effect of testosterone explains the possibility of masculinization of the female fetus following administration to pregnant women of androgenic hormones.
- At birth:
Sexual hormones (testosterone and estradiol) could respectively prepare the hypothalamus for a non-cyclic or cyclic activity. But the data are not very clear on this subject. It is necessary, in any case, to avoid the intake of hormones by new-born babies and infants.
- At puberty:
Under the influence of the pituitary gland, itself controlled by the hypothalamus, the testes increase testosterone secretion. Testosterone and its active metabolite dihydrotestosterone elicit the development of the primary sexual characters penis, seminal vesicles, prostate and secondary sexual characters (tegumentary differences, behavior characteristics, modification of morphology and voice).
- Throughout life:
Testosterone maintains the integrity of the primary and secondary sexual characters and induces spermatogenesis. After castration, there is involution of the seminal vesicles and of the prostate.
Testosterone by retro-inhibition reduces the secretion of the pituitary gonadotropins.
General effects
Testosterone and to a less degree dihydrotestosterone have general effects.
- Protein anabolism: they induce an increase in weight, muscular development, in particular of the skeletal muscles.
- Growth: two mechanisms enter into competition: a stimulant effect of growth by protein anabolism. and an inhibiting effect of growth by acceleration of epiphyseal fusion; in which estradiol is also implicated.
Thus testosterone accelerates growth, but can shorten its duration. Castration induces an increase in size by absence of epiphyseal fusion.
- Bone: testosterone increases the mineralization of bone and in patients with deficiency or treated by anti-androgens, development of osteoporosis is observed.
- Hematopoiesis: testosterone, primarily via its metabolite, dihydrotestosterone, stimulates the production of erythropoietin, increasing the number of erythrocytes and of the hematocrit which is higher in men than in women. This explains why testosterone and the anabolics could be given for the treatment of certain anemias.
- Water and ion metabolism : testosterone increases salt and water retention and edema and raises calcemia.
- Sebaceous glands: outbreak of acne at puberty can be observed.
- Central nervous system: possible increase in aggressiveness.
Dissociation of the sexual and general effects
Testosterone has sexual effects and general effects, particularly a protein anabolic effect and stimulation of erythropoiesis.
Various compounds called anabolic steroids were synthesized to try to dissociate the sexual effects from the anabolic effects by keeping only this last. It was however not possible to obtain anabolic steroids without any hormonal effect.
Hormonal and anabolic activities are measured in male castrated rats: the anabolic activity by the increase in weight of the levator muscle of the anus and the hormonal activity by the increase in the weight of the seminal vesicles. More a compound has an important effect on the levator muscle and a low effect on the seminal vesicles, more it is regarded as devoid of hormonal activity.
Anabolic steroids,such as nandrolone, trenbolone and norethandrolone, which are norsteroid derivatives where the methyl group in the19 position is replaced by an hydrogen, have properties similar to those of testosterone, but with less sexual effects because, in theory, they are not metabolized into active products by the 5-alpha-reductase enzyme.
Notice
Dehydroepiandrosterone, DHEA, mainly secreted by the adrenal cortex, is a precursor of androstenedione. It has a low androgenic effect. Its plasma concentration lowers with age. This fact suggeststhat DHEA could have a protective role against various disorders linked to ageing, but this is not clearly documented. The administration of DHEA to women having an adrenocortical insufficiency improved their overall condition and their sexuality. DHEA could also reduce the postmenopausal loss of bone. In animals, DHEA restores impaired functions of lymphocytes T. It remains to determine if, when DHEA is used over the long term, its possible beneficial effects override its possible adverse effects..
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