BETA-ENDORPHIN, BUT NOT OXYTOCIN, SUBSTANCE-P OR VASOACTIVE-INTESTINAL POLYPEPTIDE, CONTRIBUTES TO PROGESTERONE-INDUCED PROLACTIN SECRETIONIN MONKEYS

Progesterone (P) stimulates prolactin secretion through a neural mecha nism in estrogen (E)primed female monkeys. Several peptides, including beta-endorphin (BE), oxytocin (OT), substance P (SP) and vasoactive i ntestinal polypeptide (VIP) are potential prolactin stimulatory factor s and could mediate the effect of P. We hypothesized that the antagoni sm of a pivotal peptidergic neural system would block P-induced prolac tin secretion and that the function of a pivotal peptidergic system wo uld be altered by changes in gonadal steroid concentrations. Therefore it was of interest (1) to examine the effect of infusion of antagonis ts to these peptides on P-induced prolactin secretion, and (2) to dete rmine BE, OT, SP and VIP levels in the hypothalamus of monkeys of vari ous reproductive states. For the antagonist studies, female monkeys (n = 8) were spayed, adapted to a vest and tether remote sampling system and catheterized prior to antagonist challenges. E-primed monkeys rec eived P injections 48 h prior to antagonist administration. Prolactin increased within 36-48 h of P injection. All antagonist challenges wer e administered in varying doses during the P-induced prolactin elevati on and blood samples were collected every 10 min for prolactin determi nations. The opiate antagonist, naloxone (n = 5), reduced serum prolac tin in a dose-related manner with a mean IC50 of 1.5 +/- 0.6 mu g/kg/m in. The OT (n = 4), SP (n = 4) or VIP (n = 4) antagonists did not redu ce serum prolactin in a dose-related manner. We previously reported th at the hypothalamic content of OT is increased by ovarian hormones. To determine whether the hypothalamic content of BE, SP or VIP was relat ed to gonadal status, the peptide levels in 4 hypothalamic regions of monkeys in various physiological states were measured. BE (ng/mg prote in) in the medial basal hypothalamus (MBH) was significantly greater i n adult females (17.7 +/- 6.9; n = 6) as compared to spayed females (0 .6 +/- 0.2; n = 3) and juvenile females (1.8 +/- 1.1; n = 3). Hypothal amic content of SP in the preoptic area and mammillary bodies, but not the MBH, was significantly greater in gonadal intact females than spa yed females. VIP content (pg/mg protein) was not significantly differe nt between adult, spayed and juvenile females nor between adult and ju venile males in any hypothalamic area. Taken together these results su pport a pivotal role for BE in the neural regulation of P-induced prol actin secretion. The involvement of OT, SP, and VIP in a specific mann er at the pituitary level is not indicated.