Androgens (male sex hormones) play a key role in the development and function of the male reproductive system. They are furthermore responsible for the development of skeletal muscle mass, bone density, and erythropoiesis. Testosterone is the main androgen and anabolic steroid in male individuals, in whom it is secreted primarily by Leydig cells in the testicles. In female individuals, testosterone acts as an estrogen precursor and is secreted by theca interstitial cells in the ovaries. Other androgens include androstenedione and dehydroepiandrosterone (DHEA), which are secreted in the adrenal cortex. The production of androgens is controlled by the hypothalamic-pituitary-gonadal axis (HPG axis), whose function can be impaired by a deficiency or excess of testosterone. The clinical manifestations of these dysfunctions depend on the stage of development in which the imbalance occurs. Testosterone deficiency during embryonic development leads to the feminization of the male external genitalia. In the prepubescent phase, it can cause hypogonadism and delayed puberty associated with delayed constitutional growth. After puberty, testosterone deficiency can cause infertility. Synthetic androgens (anabolic-androgenic steroids) are used to treat the effects of testosterone deficiency (e.g., delayed puberty) and diseases associated with muscle loss (e.g., cancer, acquired immunodeficiency syndrome). Long-term effects of anabolic-androgenic steroids, frequently seen in individuals who misuse them to promote muscle growth, include liver and kidney damage, cardiomegaly, behavioral changes (e.g., paranoia, aggression), and hypogonadism.
For more information on androgens and their clinical relevance, see the articles on “ ,” " ,” “ ,” “ ,” and “ .”
|Overview of androgens|
Overview of androgen synthesis
- The hypothalamus secretes gonadotropin-releasing hormone (GnRH) in pulses.
- GnRH stimulates the anterior pituitary cells to secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
- LH stimulates Leydig cells to produce testosterone.
- FSH stimulates Sertoli cells to release:
- A stimulus triggers the secretion of CRH, leading to increased secretion of ACTH by the pituitary gland.
- ACTH stimulates the conversion of cholesterol into pregnenolone in the adrenal cortex.
- Enzymatic pathways trigger DHEA and androstenedione production in the zona reticularis.
- Androstenedione is converted into testosterone, which is then transformed into dihydrotestosterone via 5α-reductase.
- Aromatase converts testosterone into estradiol and androstenedione, which is then transformed into estrone.
Feedback control mechanisms
- Central regulation: The release of GnRH during puberty stimulates the secretion of FSH, LH, and sex hormones.
- Peripheral regulation: via feedback inhibition of GnRH, FSH, and LH secretion by androgens and inhibin
- Sex hormone-binding globulins (SHBGs)
The testosterone and estrogen precursors DHEA and androstenedione are produced in the adrenal cortex in both male and female individuals. Testosterone is produced by Leydig cells in the testicles and, to a lesser degree, by the theca interstitial cells in the ovaries.
AnDRostenedione is produced by the ADRenal glands and TESTostetone by the TESTicles.
- Definition: synthetic derivatives of testosterone
- Primary hypogonadism, delayed puberty in boys, hypogonadotropic hypogonadism, gonadotropin and luteinizing hormone-releasing hormone deficiency, pituitary-hypothalamic axis dysfunction, muscle mass loss in cancer and acquired immunodeficiency syndrome
- Anabolic steroids are sometimes misused as performance-enhancing drugs by athletes.
- Mechanism of action: activate androgen receptors
- Behavioral changes: aggressive behavior
- Cardiovascular: coronary heart disease, cardiomyopathy, hypertension, stroke, dyslipidemia (↑ LDL, ↓ HDL)
- Hepatic: cholestatic jaundice, hepatic neoplasms, cysts
- Renal: kidney failure
- Infections (from sharing needles in misuse): HIV, hepatitis B
- Dermatological: acne
- Hematologic: ↑ hemoglobin and hematocrit
- Musculoskeletal: tendon rupture, premature bone maturation and closure of epiphyseal plates
Clinical significance of androgens
- Androgen-secreting tumors
- Male pattern balding
- For information on drugs influencing the function of the HPG axis and androgens see “ .”