Biology of Androgens and Estrogens - Essay Example

Biology of Androgens and Estrogens Introduction Androgens, such as testosterone, are primarily produced in the testes, but physiologically significant amounts can be synthesized by the adrenal cortex as well. The primary female sex hormone is estradiol, a member of the estrogen family, produced by the ovaries and placenta. These hormones provide the endocrine identity of sexual phenotypes through there actions. Research into endocrine biology has provided newer insights into the mechanisms, functions, biology, and physiology. It would be worthwhile to briefly examine evidence from current literature to see how beliefs about these two hormones have modified. Androgens In the males androgens produced by the testes and adrenal cortex contribute to the male sex hormones circulating in the blood. Adrenal androgens normally have little physiological effect other than a role in development before the start of puberty in both girls and boys. This is because the male sex hormone activity of the adrenal androgens is weak. Androgens regulate male secondary sexual characteristics and can cause virilizing symptoms in women. Normally androgens are secreted mainly from the male testes, but moderate amount is also secreted from the adrenal gland. Normally adrenal androgens have a minimal effect in males whose sexual characteristics are predominately determined by gonadal steroids such as testosterone. On the contrary, in disease states in females, several androgen-like effects, such as, sexual hair, are largely mediated by adrenal androgens. The principal adrenal androgens are DHEA, androstenedione, and 11-hydroxyandrostenedione. DHEA and androstenedione are weak androgens and exert their effects via conversion to the potent androgen testosterone in extraglandular tissues. DHEA also has poorly understood effects on the immune and cardiovascular systems. Adrenal androgen formation is regulated by ACTH, not by gonadotropins, thus are suppressed by exogenous glucocorticoid administration. The male reproductive system regulates sexual differentiation, virilization, and the hormonal changes that accompany puberty, ultimately leading to spermatogenesis and fertility. Under the control of the pituitary hormones, namely, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), the Leydig cells of the testes produce testosterone and germ cells are nurtured by Sertoli cells to divide, differentiate, and mature into sperm (Holdcraft, RW. and Braun, RE., 2004).. Estrogens Steroidal estrogens arise from androstenedione or testosterone by aromatization of the A ring. The reaction is catalyzed by a cytochrome P450 monooxygenase enzyme complex. The ovaries are the principal source of circulating estrogen in premenopausal women, with estradiol being the main secretory product. Gonadotropins, acting via receptors that couple to the Gs-adenylyl cyclase-cyclic AMP pathway, increase the activities of aromatase. The follicular theca cells, under control of LH, produce androgens that diffuse to the follicular granulosa cells, where they are converted to estrogens via an FSH-supported aromatization reaction. Estrogens are endogenous hormones that produce numerous physiological actions. In women, these include developmental effects, neuroendocrine actions involved in the control of ovulation, the cyclical preparation of the reproductive tract for fertilization and implantation, and major actions on mineral, carbohydrate, protein, and lipid metabolism. Estrogens also have important actions in males, including effects on bone, spermatogenesis, and behavior. In postmenopausal women, the principal source of circulating estrogen is adipose tissue stroma, where estrone is synthesized from dehydroepiandrosterone secreted by the adrenals. In men, estrogens are produced by the testes, but extragonadal production by aromatization of circulating C19 steroids accounts for most circulating estrogens. Thus, the level of estrogens is regulated in part by the availability of androgenic precursors. Estrogenic effects most often have been attributed to circulating hormones, but locally produced estrogens also may have important actions. On the other hand, there are interrelations between estrogens and androgens. Following spermatogenesis, the second primary function of the testes is steroidogenesis. Steroidogenesis is the production of the steroid hormones, mainly testosterone. Testosterone is then converted to dihydrotesterone (DHT), the most biologically active androgen, and to estradiol, the most biologically active estrogen (Moll GW Jr, Rosenfield RL, Helke JC., 1981). Beliefs There are certain beliefs prevalent about interrelationhips between estrogens and androgens. For example, estrogens may be produced from androgens by the actions of aromatase or from estrogen conjugates by hydrolysis. Estrogens are largely responsible for pubertal changes in girls and secondary sexual characteristics. They cause growth and development of the vagina, uterus, and fallopian tubes, and contribute to breast enlargement. They also contribute to molding the body contours, shaping the skeleton, and causing the pubertal growth spurt of the long bones and epiphyseal closure. Growth of axillary and pubic hair, pigmentation of the genital region, and the regional pigmentation of the nipples and areolae that occur after the first trimester of pregnancy are also estrogenic actions. Androgens may also play a secondary role in female sexual development. It is also believed that estrogens appear to play important developmental roles in males. In boys, estrogen deficiency diminishes the pubertal growth spurt and delays skeletal maturation and epiphyseal closure so that linear growth continues into adulthood. Estrogen deficiency in men leads to elevated gonadotropins, macroorchidism, and increased testosterone levels and also may affect carbohydrate and lipid metabolism and fertility in some individuals (Kaufman, JM and Vermeulen, A., 2005). The decline in ovarian function is associated with a decrease in estrogen secretion and a concomitant increase in LH and FSH, which is characteristic of menopausal women. The elevated LH stimulates ovarian stroma cells to continue producing androstenedione. Estrone, derived almost entirely from the peripheral conversion of adrenal and ovarian androstenedione, becomes the dominant estrogen. It is believed that because the ratio of estrogens to androgens decreases, some women exhibit hirsutism, which results from androgen excess (Liu, PY., Death, AK., and Handelsman, DJ., 2003). Investigations of the sexual activity of women during and following natural menopause appear to have provided little support for the widely accepted belief that androgens rather than estrogens are the major determinants of women sexual interest. In most studies reduction in interest among menopuasal women along with vasomotor symptoms and atrophic vaginitis responded to estrogen alone, thus placing a great question mark against the belief of androgen:estrogen balance mechanism. Few studies however report positive effects with addition of androgen when sexual drive is low (Handelsman, DJ., 2006). Wierman et al. in their recent article "Androgen Therapy in Women: An Endocrine Society Clinical Practice Guideline" provide a research-based guidelines for androgen therapy in women. The current study does not recommend androgen therapy in women since the clinical syndrome of androgen deficiency is not encountered in women. The evidence is inadequate in favor of this generally advisable androgen therapy in women due to believed deficiency, except in few early cases of surgical menopause on a short-term basis. There is no pathological or clinical condition of androgen deficiency in females. Research in this area has still some gaps in terms of eliciting the clinical syndrome of androgen deficiency in females, and there is not much evidence to indicate androgen therapy. It is widely held belief that the sexual dysfunction, cognition, mood, bone disorders, cardiovascular function, body composition, muscle strength and function may result from androgen, and therefore, androgen replacement in these estrogen deficient individuals is indicated. However recent research does not indicate such to be true. Further research has been recommended (Wierman, ME. et al., 2006) Lastly in a study by Weiner et al., the authors have experimented on a series of patients with polycystic ovarian syndrome. This study reveals many interesting facts about estrogens and androgens. It has been theorized that deviant gonadal hormones contribute to the dysfunctional mood states in women through activational effects in the brain. Augmented levels of androgens have been implicated in clinical mood disorders in women. There are abundant estrogen and androgen receptors in brain. Females those who have premenstrual syndrome (PMS) and who are depressed show increased free testosterone levels. Those without PMS show decreased premenstrual testosterone levels. In other stages of menstrual cycle, testosterone levels correlate with mood states. Both in preparatum and postpartum women, testosterone is related with anger and depression. Menopausal women treated with testosterone or with testosterone with estrogen lead to high androgen in the serum and cause hostility (Weiner, CL., Primeau, M., and Ehrmann, DA., 2004). Discussion: A synthesis of already established findings indicate that a balance of estrogen and androgen play in sexual development and function of both men and women with androgen being predominant in men and estrogen being predominant in women. Adrenal glands in particular synthesize androgen and estrogen in females and males respectively, and many manifestations occur through receptor in brains. Although the popular belief is that menopause and andropause are nothing but declining estrogen and androgen respectively, recent evidence do not suggest that systemic effects of androgen and estrogen deficiencies in males and females do not directly correlate with estrogen and androgen predominance in them leading to changes in cardiovascular, mood, cognition, or bones in these states in . Moreover, studies also reveal that in females with androgenic excess in different parts of their lives respond in different manners in terms of mood and behaviour. Thus these effects cannot be stereotyped to a single function, rather these depend on different other parameters such as receptor binding in different organs (Toran-Allerand, CD., 2004). Conclusion: Androgens and estrogens are biological enigma in the sense that they determine the sexual development. Apart from the secondary sexual characteristics, and now it is definitely known that both males and females possess estrogens and androgens and the expression depends upon the predominance of one over the other. Many disease conditions have been studied including physiological states especially in females that indicate they work through receptors located in different organs, but even the same subject depending on varied estrogenic status, androgen will have different organ-specific manifestations and vice versa. Although these are facts, pathological effects of androgen deficit in estrogen deficient states are not yet proved so as to warrant androgen replacement. Further research is underway. Reference Handelsman, DJ., (2006). The Rationale for Banning Human Chorionic Gonadotropin and Estrogen Blockers in Sport. J. Clin. Endocrinol. Metab.; 91: 1646 - 1653. Holdcraft, RW. and Braun, RE., (2004). Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids. Development; 131: 459 - 467. Kaufman, JM and Vermeulen, A., (2005). The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications. Endocr. Rev.; 26: 833 - 876. Liu, PY., Death, AK., and Handelsman, DJ., (2003). Androgens and Cardiovascular Disease. Endocr. Rev.; 24: 313 - 340. Moll GW Jr, Rosenfield RL, Helke JC., (1981). Estradiol-testosterone binding interactions and free plasma estradiol under physiological conditions. J Clin Endocrinol Metab;52:868-74. Toran-Allerand, CD., (2004). Minireview: A Plethora of Estrogen Receptors in the Brain: Where Will It End Endocrinology; 145: 1069. Weiner, CL., Primeau, M., and Ehrmann, DA., (2004). Androgens and Mood Dysfunction in Women: Comparison of Women With Polycystic Ovarian Syndrome to Healthy Controls. Psychosom Med; 66: 356 - 362. Wierman, ME., Basson, R., Davis, SR., Khosla, S., Miller, KK., Rosner, W., and Santoro, N., (2006). Androgen Therapy in Women: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab.,; 91: 3697 - 3710. Read More