OVARIAN-STEROID REGULATION OF TRYPTOPHAN-HYDROXYLASE MESSENGER-RNA EXPRESSION IN RHESUS MACAQUES

Progesterone (P) stimulates prolactin secretion through an unknown neu ral mechanism in estrogen (E)-primed female monkeys, Serotonin is a st imulatory neurotransmitter in prolactin regulation, and this laborator y has shown previously that E induces progestin receptors (PR) in sero tonin neurons. Therefore, we questioned whether E and/or E+P increased serotonin neural function. The expression of mRNA for tryptophan hydr oxylase (TPH) was examined in ovariectomized (spayed) control, E-treat ed (28 d), and E+P-treated monkeys (14 d E and 14 d E+P) using in situ hybridization and a 249 bp TPH cRNA probe generated with RT-PCR (n=5 animals/group). Densitometric analysis of film autoradiographs reveale d a ninefold increase in TPH mRNA in E-treated macaques compared to sp ayed animals (p <0.05). With supplemental P treatment, TPH mRNA signal was increased fivefold over spayed animals P <0.05), but was not sign ificantly different compared to E-treated animals. These results were verified by grain counts from photographic emulsion-coated slides. The re were significantly higher single-cell levels of TPH mRNA in seroton ergic neurons of the dorsal raphe in E- and E+P-treated groups (p < 0. 05), These data indicate that E induces TPH gene expression in nonhuma n primates and that the addition of P has little additive effect on TP H gene expression, Thus, the action of P on prolactin secretion is pro bably not mediated at the level of TPH gene transcription. However, be cause P increases raphe serotonin content in E-primed rodents, the pos sibility remains that P may have other actions on post-translational p rocessing or enzyme activity.