Effects of progesterone on prolactin, hypothalamic β-endorphin, hypothalamic substance p, and midbrain serotonin in guinea pigs

Unlike rats, but similar to primates, guinea pigs exhibit prolonged function of the corpus luteum and elevated progesterone secretion after ovulation. The gonadotropins, estrogen (E) and progesterone (P) have been examined throughout the guinea pig estrous cycle. However, neither prolactin secretion nor its regulation by steroid hormones has been characterized, perhaps due to the lack of a specific radioimmunoassay. β-Endorphin (BE), substance P (SP), and serotonin (5-HT) increase prolactin secretion in rats and monkeys. BE and SP neurons in guinea pigs and 5-HT neurons in monkeys contain progestin receptors which could mediate neuroendocrine effects of steroid hormones. Therefore, the effects of E and P on prolactin, BE, SP, and 5-HT and its metabolite 5-HIAA were examined in guinea pigs which were ovariectomized, E treated (28 days), and E + P treated (14 days E + 14 days E + P). The rat NB2 lymphoma cell line was used as a bioassay for serum prolactin. BE and SP levels were measured by radioimmunoassay in four hypothalamic areas: the preoptic region (POA), the mediobasal hypothalamus (MBH), the dorsomedial hypothalamus (DMH), and the mamillary bodies (MB). 5-HT and 5-HIAA were measured in the midbrain raphe area by high-pressure liquid chromatography. E alone had little effect on serum prolactin levels, but E + P significantly increased prolactin as compared with ovariectomized controls. The BE levels increased with E treatment and remained elevated with E + P treatment in MBH and POA. The BE content was stimulated in DMH and MB by E + P treatment and not with E alone. The SP content in MBH, DMH, and MB increased in E-treated guinea pigs. However, SP then decreased upon addition of P to the E regimen. The 5-HT and 5-HIAA levels were similar in ovariectomized and E-treated groups. Addition of P to the E treatment significantly increased 5-HT and 5-HIAA levels relative to the E only treatment. These studies show that P increases prolactin secretion in E-primed guinea pigs in a manner similar to primates. 5-HT and 5-HIAA increased with P addition to an E regimen, but not with E alone. BE and SP both increase with E treatment, but BE remains elevated upon addition of P, whereas SP is suppressed by P. Thus, the steroid regulation of BE and 5-HT, but not SP, is consistent with a role in P-induced prolactin secretion in guinea pigs.