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Volume 16, Number 21, Issue of November 1, 1996 pp. 7021-7029
Copyright ©1996 Society for Neuroscience

Ovarian Steroid Regulation of Tryptophan Hydroxylase mRNA Expression in Rhesus Macaques

Received May 22, 1996; revised July 9, 1996; accepted Aug. 7, 1996.

Melanie Pecins-Thompson, Nancy A. Brown, Steven G. Kohama, and Cynthia L. Bethea

Divisions of Reproductive Sciences and Neuroscience, Oregon Regional Primate Research Center, Beaverton, Oregon 97006, and Department of Physiology, Oregon Health Sciences University, Portland, Oregon 97201

Progesterone (P) stimulates prolactin secretion through an unknown neural mechanism in estrogen (E)-primed female monkeys. Serotonin is a stimulatory neurotransmitter in prolactin regulation, and this laboratory has shown previously that E induces progestin receptors (PR) in serotonin neurons. Therefore, we questioned whether E and/or E+P increased serotonin neural function. The expression of mRNA for tryptophan hydroxylase (TPH) was examined in ovariectomized (spayed) control, E-treated (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 revealed a ninefold increase in TPH mRNA in E-treated macaques compared to spayed animals (p < 0.05). With supplemental P treatment, TPH mRNA signal was increased fivefold over spayed animals (p < 0.05), but was not significantly different compared to E-treated animals. These results were verified by grain counts from photographic emulsion-coated slides. There were significantly higher single-cell levels of TPH mRNA in serotonergic 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 nonhuman primates and that the addition of P has little additive effect on TPH gene expression. Thus, the action of P on prolactin secretion is probably not mediated at the level of TPH gene transcription. However, because P increases raphe serotonin content in E-primed rodents, the possibility remains that P may have other actions on post-translational processing or enzyme activity.

Key words: tryptophan hydroxylase mRNA; progesterone; estrogen; serotonin; monkey; dorsal raphe




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