THE DIRECT PITUITARY EFFECT OF TESTOSTERONE TO INHIBIT GONADOTROPIN-SECRETION IN MEN IS PARTIALLY MEDIATED BY AROMATIZATION TO ESTRADIOL

In men, administration of exogenous testosterone (T) exerts direct neg ative 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 est radiol (E(2)) or dihydrotestosterone (DHT) is required. We assessed th e biological activity of serum luteinizing hormone (LH) and follicle-s timulating hormone (FSH), as well as immunoactivity. Blood samples wer e drawn before, during, and after a continuous, 72-hour i.v. infusion of T(15 mg/day), E(2) (90 mu g/day), or DHT (500 mu g/day). Each of th ese doses is twice the daily production rate of the steroid. Each man received each of the three steroid infusions. We studied four men, age s 23-35, with idiopathic hypothalamic hypogonadism (IHH), who were tre ated with pulsatile gonadotropin releasing hormone (GnRH) until their gonadotropins reached the normal range. Serum levels of T, E(2), DHT, and levels of immunologically active and biologically active LH and FS H were measured. We found that administration of each steroid increase d serum levels of the infused steroid to the upper physiologic range. Administration of T or E(2) resulted in decreased mean levels of biolo gically and immunologically active LH and FSH; administration of DHT d id not alter gonadotropin secretion. These data suggest that some of t he direct effect of T at the pituitary level in men is mediated by E(2 ), whereas peripherally formed DHT may not play an important role in t his process.