The Direct Pituitary Effect of Testosterone to Inhibit Gonadotropin Secretion in Men Is Partially Mediated by Aromatization to Estradiol

Abstract

ABSTRACT: In men, administration of exogenous testosterone (T) exerts direct negative feedback effects at the pituitary as well as at the hypothalamic level. This study was undertaken to determine whether T itself causes the inhibitory effects on the pituitary, or whether conversion to estradiol (E2) or dihydrotestosterone (DHT) is required. We assessed the biological activity of serum luteinizing hormone (LH) and follicle‐stimulating hormone (FSH), as well as immunoactivity. Blood samples were drawn before, during, and after a continuous, 72‐hour i.v. infusion of T (15 mg/day), E2 (90 μg/day), or DHT (500 μg/day). Each of these doses is twice the daily production rate of the steroid. Each man received each of the three steroid infusions. We studied four men, ages 23–35, with idiopathic hypothalamic hypogonadism (IHH), who were treated with pulsatile gonadotropin releasing hormone (GnRH) until their gonadotropins reached the normal range. Serum levels of T, E2, DHT, and levels of immunologically active and biologically active LH and FSH were measured. We found that administration of each steroid increased serum levels of the infused steroid to the upper physiologic range. Administration of T or E2 resulted in decreased mean levels of biologically and immunologically active LH and FSH; administration of DHT did not alter gonadotropin secretion. These data suggest that some of the direct effect of T at the pituitary level in men is mediated by E2, whereas peripherally formed DHT may not play an important role in this process.