Androgen deficiency in menMar 14, Author: Androgens are produced primarily from the toxic anabolic steroids glands and the ovaries. However, peripheral tissues male androgen as fat and skin also qndrogen roles in converting weak androgens to more potent ones. Androgen excess can affect different tissues and organs, causing variable clinical features such as acne, hirsutism, virilization, and reproductive male androgen. The endocrine glands secrete 5 androgens through a similar pathway:
Androgen - an overview | ScienceDirect Topics
Mar 14, Author: Androgens are produced primarily from the adrenal glands and the ovaries. However, peripheral tissues such as fat and skin also play roles in converting weak androgens to more potent ones. Androgen excess can affect different tissues and organs, causing variable clinical features such as acne, hirsutism, virilization, and reproductive dysfunction.
The endocrine glands secrete 5 androgens through a similar pathway: Testosterone and its biologically active metabolite dihydrotestosterone DHT are the only androgens with direct androgenic activity.
Testosterone is used as a marker of ovarian androgen secretion. However, the adrenals also contribute to circulating testosterone via peripheral conversion of androstenedione to testosterone.
DHEAS and androstenedione are not secreted by the ovaries and, therefore, are used as markers of adrenal androgen secretion. Adrenal androgen secretion is dependent on adrenocorticotropic hormone ACTH secreted by the anterior pituitary.
Both prolactin and estrogen can affect adrenal androgen production. Skin, fat, liver, and urogenital systems are important peripheral sites of androgen production. Androstenedione, and to some degree DHEA, are converted to testosterone in the skin. Of the circulating androgens, only testosterone and DHT are able to activate androgen receptors. The rest of the testosterone is produced by the peripheral conversion of androstenedione in adipose tissue.
The androgenicity depends mainly on the unbound fraction due to the high affinity of SHBG to the bound androgens.
The levels of SHBG increase and decrease based on conditions and medications. Unlike SHBG; albumin has a low affinity for sex hormones, so the albumin-bound androgens are readily available to tissues. Also, LH stimulates theca cells of the ovaries to secrete androgens; however, there is no feedback regulatory loop that controls androgen secretion in women.
Most of the circulating testosterone is metabolized in the liver into androsterone and etiocholanolone, which are conjugated with glucuronic acid or sulfuric acid and execrated in the urine as ketosteroids. Androgens induce virilization and are responsible for forming the male external genitalia in the fetus.
Their absence or the absence of androgen receptors results in a female phenotype, despite the presence of a 46 XY karyotype eg, androgen insensitivity syndrome. Androgens are also responsible for the development of the secondary sexual organs and ducts, the seminal vesicles, and the prostate. Postnatal females are not as sensitive as the fetus to androgens, which induce the growth of sexual hair, temporal balding, acne, clitoral growth, sebum production, and a deepening of the voice.
Oral androgens decrease high-density lipoprotein HDL cholesterol and increase low-density lipoprotein LDL cholesterol. With androgen excess, the extent of these changes is dependent on the level of androgens in the blood. Androgens have direct effects on different body systems and also act as precursor hormones for ovarian and extragonadal estrogen synthesis. Androgen receptors are present in a variety of tissues like skeletal muscles, skin, gastrointestinal tract, genitourinary tract, bone, brain, cardiovascular system, placenta, and adipose tissues.
Androgen actions are not completely understood in all of these tissues. Androgen receptors are distributed throughout the brain in close proximity to estrogen receptors.
The highest concentrations are present in the preoptic area of the hypothalamus. Growing evidence supports the role of androgens in physiologic levels and sexual desire.
Decreased sexual function has been reported in hyperandrogenic women receiving antiandrogens; on the other hand, administration of testosterone in women with hypoactive sexual desire disorder results in improvements in libido and sexual function. Androgens have important roles in bone mineralization either directly or through aromatization to estrogen. Lower androgen concentrations have been associated with bone loss in various age groups.
Androgen receptors are present in mammary epithelial cells in addition to estrogen and progesterone receptors. The proposed mechanisms include either direct stimulation of the androgen receptors or conversion to estradiol by the aromatase enzyme present in breast tissue. Androgens, particularly DHEA and testosterone, have been reported to protect against mammary epithelial proliferation in female monkeys.
The reverse effect was reported when the antiandrogen flutamide was given to those animals. Few data are available regarding the effects of androgens on human breasts.
Unopposed estrogen stimulation of the endometrium increases the risk of endometrial hyperplasia and eventually cancer. The proposed mechanism of androgen aromatization to estradiol may not be applicable because the aromatase expression has not been detected in normal endometrium and stromal cells. There is a great concern about the relation between sex hormones and cardiovascular events.
Women with PCOS have hyperandrogenemia and are at higher risk of cardiovascular events. Moreover, the exogenous administration of testosterone for female to male transsexual has not been associated with the increased risk of cardiovascular disease.
In the target tissues, androgens enter the cell cytoplasm by simple diffusion across the cell membrane. Once inside the cell, the androgens bind and activate the androgen receptors. The androgen-receptor complex attaches to a specific DNA site and stimulates the production of messenger RNA, which, in turn, stimulates the production of the enzymes and proteins necessary to affect androgen action. Androgen excess affects mainly the pilosebaceous unit PSU and the reproductive system.
The PSU secretes sebum and is the unit from which hair grows. Three types of hair, lanugo, vellus, and terminal hairs, exist. The fine hairs of the fetus are lanugo and the peach fuzz hair of adults is vellus hair. These hairs are fine, short, and nonpigmented. Thick and pigmented hair is referred to as terminal hair.
Those hairs of the pubic, axillary, sternal, and facial areas are responsive to androgens and those in scalp, eyelashes, and eyebrows are androgen-independent. Their prevalence depends largely on genetics. As androgen levels rise, more vellus hairs in the androgen-sensitive areas are converted into terminal hairs, resulting in hirsutism.
Androgens prolong the growth phase of hair and promote their conversion from vellus to terminal type. Sebum production from the PSU is also increased by androgens.
Acne vulgaris can be aggravated or initiated by increased androgen levels as the excess sebum production and the shedding of hyperkeratinized epithelium may occlude the hair follicle. Propionibacterium acnes proliferates and triglycerides of sebum are then hydrolyzed by the bacterial lipases to form glycerol and free fatty acids, which, together with other bacterial metabolites, cause inflammation. It is also commonly proposed that hypersensitivity of PSU to androgens is the cause of acne.
Individuals who are insensitive to androgen have less active sebaceous glands and do not develop acne. Although there has been some controversy over whether acne is common enough in androgen excess to be considered a sign of hyperandrogenemia, a study by Uysal et al indicated that it is indeed evidence of the condition.
Androgen excess is a common feature of PCOS, which is also the most common cause of anovulatory infertility. The ovarian theca cells increase their ovarian androgen production under the stimulatory activity of the raised LH levels, and in many cases, raised insulin levels. Hyperinsulinemia due to peripheral insulin resistance is often present in women with PCOS and it promotes hyperandrogenemia through the binding of insulin to the insulin-like growth factor—1 IGF-1 receptor.
Insulin mimics the action of insulin growth factor 1 IGF-1 , which augments androgen production by the theca cell in response to LH. Since insulin decreases levels of SHBG, the circulating levels of free testosterone are also increased. A retrospective study by Elhassan et al indicated that in women with androgen excess, the pattern of excess varies according to the etiology.
The investigators found, for example, increased androstenedione levels in all cases of adrenocortical carcinoma, while all ovarian hyperthecosis cases showed increased testosterone. In postmenopausal women, adrenocortical carcinoma was responsible for all occurrences of severe DHEAS and androstenedione excess, while adrenocortical carcinoma and ovarian hyperthecosis were equally responsible for severe testosterone excess.
The international incidence rate is dependent on the particular culture, but, essentially, it is similar to that of the United States. Androgen excess per se does not cause mortality or morbidity, but it is associated with insulin resistance, dyslipidemia, hypertension, and vascular diseases; [ 5 ] therefore, it is a forerunner of cardiovascular disease. Androgen excess occurs equally in all races. Congenital adrenal hyperplasia prevalence due to hydroxylase deficiency is greater among those of Ashkenazi Jewish descent.
Congenital adrenal hyperplasia occurs equally in both sexes; however, this article focuses on females. The most common causes of hyperandrogenism begin in early adolescence or in childbearing age. Androgen-producing tumors may rarely affect postmenopausal women. The climacteric ovary as a functional gonadotropin-driven androgen-producing gland.
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