Effects of 2-Bromo-Alpha-Ergocryptine on the Secretion of Pituitary Hormones in Normal Male Subjects

Abstract

It is well known that catecholamines in the hypothalamus influence the control of release of hormones by the anterior pituitary, especially that of prolactin and Gil. Catecholamines are reported to play a role as a neurotransmitter which stimulates the release of prolactin release-inhibiting factor (PIF) and/or directly to inhibit the relase of prolactin at the pituitary gland. L-dopa, the precursor of dopamine, is known to stimulate the secretion of growth hormone in man. On the other hand, although the effects of catecholamines on the release of gonadotropins and ACTH from the pituitary gland were studied by many investigators, the results are inconsistent. McCann and his coworkers reported that the release of gonadotropins was stimulated by dopamine or dopaminergic mechanism. On the contrary, Fuxe found that the dopaminergic neuron took part in inhibiting the release of gonadotropins. On the release of ACTH, the results obtained by Abe and Hiroshige were different from those by Ganong and his coworkers.Recently, the ergot alkaloid, 2-bromo-alpha-ergocryptine (CB-154, Sandoz Co.), was found to be a strong dopaminergic stimulator, to inhibit the secretion of prolactin, and to be effective in inhibiting galactorrhea.In the present study, effects of CB-154 which was used as a strong dopaminergic stimulator on plasma prolactin, LH, FSH, TSH, Gil and ACTH levels in normal male subjects are investigated.After an over-night fast, 2. 5 mg of CB-154 was orally administered 8 a.m. and blood sample was withdrawn 10 a.m. and then 100 μg of luteinizing hormone-releasing hormone (LH-RH) and 500 μg of thyrotropin-releasing hormone (TRH) was injected intravenously. After the injection, 1-arginine (0.5 g/kg b.w.) was infused into a cubital vein over 30 min. Blood was taken 15, 30, 60, 90, and 120 min following the injection of LH-RH and TRH.Plasma ACTH, GH TSH, LH, FSH and prolactin were determined by radioimmunoassay kits.The following results were obtained : 1) CB-154 inhibited not only basal plasma prolactin levels, but also the increase in plasma prolactin levels induced by TRH.2) Although the single administration of CB-154 had no effect on basal plasma LH and FSH levels, the increase in plasma gonadotropins, especially FSH, induced by LH-RH had a tendency to be enhanced by CB-154.3) CB-154 suppressed the increment of plasma TSH by TRH in normal male subjects.4) The oral administration of CB-154 had a tendency to elevate basal plasma GH levels, it did not augment the increase in plasma GH levels induced by 1-arginine.5) In a few case, CB-154 enhanced ACTH release. However, the effect of CB-154 on ACTH release was inconsistent. These results revealed that CB-154, a strong dopaminergic stimuiant, inhibits the release of TSH as well as that of of prolactin in normal male subjects, and stimulates the release of gonadotropins and of GH.