Ovarian Steroid Regulation of Tryptophan Hydroxylase mRNA Expression in Rhesus Macaques

Abstract

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 EϩP increased serotonin neural function. The expression of mRNA for tryptophan hydroxylase (TPH) was examined in ovariectomized (spayed) control, E-treated (28 d), and EϩP-treated monkeys (14 d E and 14 d EϩP) using in situ hybridization and a 249 bp TPH cRNA probe generated with RT-PCR (n ϭ 5 animals/group). Densitometric analysis of film autoradiographs revealed a ninefold increase in TPH mRNA in E-treated macaques compared to spayed animals ( p Ͻ 0.05). With supplemental P treatment, TPH mRNA signal was increased fivefold over spayed animals ( p Ͻ 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 EϩP-treated groups ( p Ͻ 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.

Effects of Ovarian Steroids and Raloxifene on Proteins that Synthesize, Transport, and Degrade Serotonin in the Raphe Region of Macaques

“…There was no difference in TPH protein between groups treated with estrogen alone or estrogen þ progesterone. This confirms our earlier observation with additional animals (Pecins- Thompson et al, 1996). In addition, there was no significant difference in the signal corresponding to phosphorylated TPH (Figure 4, bottom) nor in the calculated ratio of phosphorylated TPH to TPH protein (data not illustrated).…”

“…Commercially available antibodies do not discriminate between the translated proteins and provide an indication of total TPH. We demonstrated that 1 month (mo) of estrogen, with or without supplemental progesterone, increased TPH-1 mRNA levels in the dorsal raphe of macaques (Pecins-Thompson et al, 1996). Recently, we have found that TPH-2 is regulated in a similar manner (unpublished).…”

“…We previously showed that estrogen alters the expression of TPH-1, SERT, 5HT1A, and MAO-A genes in the dorsal raphe (Pecins-Thompson et al, 1996;Gundlah et al, 2001a). We have recently found that TPH-2 mRNA is robustly expressed in the monkey raphe, and it is significantly increased by estrogen and estrogen þ progesterone in a manner similar to .…”

Glucocorticoid modulation of tryptophan hydroxylase-2 protein in raphe nuclei and 5-hydroxytryptophan concentrations in frontal cortex of C57/Bl6 mice

“…7,[21][22][23][24][25][26][27][28][29][30] While these studies demonstrated hormonal regulation of serotonin synthesis, the existence of TPH isoforms was not yet appreciated and therefore not studied. With the identification of TPH2, 4 it has become important to understand the effects of hormones on the individual isoforms.…”

Menstrual cycle phase modulates cognitive control over male but not female stimuli

“…Buffet et al, 2001) have verified that the concentrations and ratios of circulating sex hormones oscillate throughout the menstrual cycle and influence the central nervous system (CNS) in a large number of varied ways the menstrual cycle effects reported here may be related to hormonal influences. Cholinergic (Gibbs et al, 1998;Lucey et al, 1991;Tseng et al, 1997), glutamatergic (Gazzaley et al, 1996 andWoolley et al, 1997), GABAergic (Murphy et al, 1998), serotonergic (Biegon et al, 1983;Moses et al, 2000;Pecins-Thompson et al, 1996;Sumner and Fink, 1997) noradrenergic (Tseng et al, 1997), and dopaminergic neurotransmitter (Pasqualini et al, 1995) and (Pasqualini et al, 1996) systems all respond to sex hormones. Dopamine is of particular interest here given its role in both response inhibition (Hester et al, 2004) and the ACC error response (Holroyd and Coles, 2002).…”