Testosterone Physiologic Effect
Testosterone regulation depends on the hypothalamic-pituitary-gonadal (HPG) axis (Figure 1). The hypothalamus secretes gonadotropin-releasing hormone (GnRH), which stimulates the anterior pituitary to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH stimulates Sertoli cell function and spermatogenesis. LH stimulates the interstitial testicular Leydig cells to produce testosterone. This HPG axis is regulated via a negative feedback loop. As its production increases, testosterone inhibits the frequency and amplitude of GnRH released from the hypothalamus, thus resulting in decreased FSH and LH production and decreased stimulation of spermatogenesis and testosterone production. Testosterone secretion occurs in a circadian pattern. There are approximately 6 bursts of testosterone secretion a day; circadian testosterone production patterns with an early morning high and early evening low.
Testosterone's physiological effect is exerted by the conversion of testosterone to dihydrotestosterone (DHT) by 5α-reductase enzymes or to estradiol by aromatase. Testosterone and DHT both bind to androgen receptors throughout the body, producing physiologic effects of testosterone on muscle, bone, and other organs. Testosterone circulates freely in the blood and binds to different types of globulins. Approximately 1%–2% of testosterone circulates freely in the blood, and 98%–99% of testosterone binds to albumin (40% to 50%) and sex hormone-binding globulin (SHBG). The SHBG is tightly bound to testosterone. Therefore, the biologically available testosterone that produces the physiologic effect is primarily the free and albumin bound testosterone, which is known as the bioavailable testosterone (BAT).
Physiologic effects of testosterone include the maintenance of reproductive tissue, spermatogenesis, sexual function, lean muscle mass production, nitrogen retention, bone mass stability, sebum production, axillary and body hair growth, and erythropoiesis. The Institute of Medicine (IOM) summarized key outcomes associated with a decreased testosterone physiological effect in the body (Table 1).
Journal for Nurse Practitioners. 2012;8(10):778-786. © 2012 Elsevier Science, Inc.