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Human Gonadotropins
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Gonadotropins and steroidogenesis (2022)
Estrogens and progestogens
The sex steroids are androgen, estrogens, and progestogens. They are all made from the root steroid cholesterol (Fig. 14.1). Cholesterol is always thought about in a negative sense, such as in vascular blockage, cranial vascular accident, and myocardial infarction. On the positive side, cholesterol is the root or mother steroid; there would be no sex steroids without cholesterol. As shown in Fig. 14.1, cholesterol is made from cytoplasmic Acetyl CoA. The constituents come from the oxidation of sugars or oxidative degradation of fatty acids as mitochondrial acetyl CoA is transferred to the cytoplasm. Cholesterol carbons are numbered to a convention used in the naming and numbering of all steroids.
There are multiple types of progestogens. All these can be identified as 21-carbon steroids. Progestogens include progesterone and 17α-progesterone, the two biologically active natural progestogens (Fig. 14.2). Synthetic progestogen agonists used by steroid manufacturers include norpregnene and norethisterone, among others (Fig. 14.2). Similarly, there is not just one androgen. Natural androgens include testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA-sulfate, and dihydrotestosterone. Androstanalone is an example of a commercial androgen agonist. All androgens are characteristically 19-carbon steroids. There are three natural forms of estrogen; these are estrone or E1, estradiol or E2, and estriol or E3 (Fig. 14.2). To help remember their names, structures, and numbers, consider the following Fig. 14.3, estrONE or E1 contains one hydroxyl group, estraDIol or E2 contains two hydroxyl groups, and esTRIol or E3 contains three hydroxyl groups. Estrogens have two characteristics; are always 18 carbon steroids and always have an aromatized ring A.
All three estrogens are aromatized or made by the same aromatase enzyme (Fig. 14.3) but are made from different androgen substrates. Estrone (E1) is made by aromatase action on androstenedione, estradiol (E2) by aromatase action on testosterone, and estriol (E3) by aromatase action on 16α-dehydroxyandostenedione. Ethinylestradiol is an example of a commercial estrogen agonist.
While detailed structures of the steroids and their synthesis pathways are not presented here, however, the basic features of sex steroids, progestogens 21 carbon structures, androgens 19 carbon structures, and estrogens 18 carbon structures with an aromatized ring are discussed.
*Sex steroid synthesis by the ovary
*Sex steroid synthesis in pregnancy
*Functions of sex steroids
*Sex steroid functions in the menstrual cycle and pregnancy
Male steroidogenesis
We consider the essential cells of the testis, Fig. 14.11. The Leydig cells are the site of action of LH or human chorionic gonadotropin (hCG) and the Sertoli cells are the sites of action of follicle-stimulating hormone (FSH). LHs (or hCGs) are the pituitary hormones that promote steroidogenesis in males, while testosterone is made in Leydig cells, and dihydrotestosterone is made in Sertoli cells (Fig. 14.11).
GnRH is released in pulses by the hypothalamus including LH (hCG) and FSH. LH (or hCG) directly promotes cholesterol side-chain cleavage enzyme in Leydig cells, changing cholesterol to pregnenalone (Fig. 14.12). The pregnenalone is converted to androstenedione like in theca cells in females, and then to testosterone (Fig. 14.12). The testosterone can be aromatized directly in the Leydig cells to make estradiol. Testosterone enters the blood from this point and gets transferred to the testis seminiferous tubules. Some testosterone gets transferred to Sertoli cells (Fig. 14.12), where it undergoes reduction to make the more active androgen, dihydrotestosterone and is aromatized to estradiol. Testosterone feeds back to the hypothalamus modulating GnRH pulses. The major difference between steroidogenesis in the male and female gonads is that testosterone production is continuous in the postpubertal male and not menstrual-cyclic as a steroid in the postpubertal female.
Functions of androgens in males
As shown in Table 14.1, testosterone is the principal steroid produced by the testes on a constant, non-cyclic basis. Testosterone, complemented by dihydrotestosterone has the following functions in the adult male:
1. Promotion of sperm development in seminiferous tubules.
2. Substrate for the synthesis of more potent androgen dihydrotestosterone, and for aromatization to estradiol.
3. Secondary sexual characteristics in males, increase bone and muscular masses, and hair growth.
4. Libido development and promotion of penile erection.
5. Promotes adult male mental and physical energy. Questionable research suggests that it may have a role in the maintenance of cardiovascular health, and in risk-taking.
Prenatally, testosterone is significant in genital virilization, development of the prostate and seminal vesicles, and in gender identity. In the male fetus, testosterone promotes the differentiation of the Wolffian duct to form an epididymis and vas deferens.
During puberty, testosterone causes enlargement of the sebaceous glands, promotes male libido, and penile enlargement, and increases facial hair, chest hair, leg hair, axillary hair, and jaw growth.
Functions of estrogens males
The function of estradiol formed normally in males is far from sure. Evidence suggests that estradiol has a role in the following:
1. Growth of penis
2. Development of testicles
3. Growth of hair
4. Deepening voice in men
5. Maturations of sperm.
More research is needed to confirm the exact function of estradiol in men.
