Progesterone suppresses tyrosine hydroxylase messenger ribonucleic acid levels in the arcuate nucleus on proestrus.

Abstract

This study examined the intracellular mechanisms for the regulation of tyrosine hydroxylase in the tuberoinfundibular dopaminergic neurons of cycling female rats. It also evaluated the hormonal influences that contribute to the control of this enzyme on proestrus. Tyrosine hydroxylase messenger RNA (mRNA) levels in the arcuate nucleus of the hypothalamus were assessed by in situ hybridization. Tyrosine hydroxylase activity in the stalk-median eminence was determined from the in vitro or in vivo rate of 3,4-dihydroxyphenylalanine (DOPA) accumulation after inhibiting DOPA decarboxylase with brocresine or m-hydroxybenzylhydrazine, respectively. Tyrosine hydroxylase mRNA levels and in vitro DOPA accumulation were similar on diestrous day 2 and proestrous mornings, but were reduced by 50% on estrus. Although circulating PRL concentrations were similar on the morning of each day of the estrous cycle, a broad preovulatory PRL surge was observed on the afternoon of proestrus. In vitro DOPA accumulation was similar at 1000 h before the PRL surge and at 1330 h during the peak phase of the PRL surge, but was reduced during the plateau phase of the PRL surge (1700 and 2200 h) coincident with the preovulatory progesterone rise and remained low on estrus. However, in vivo DOPA accumulation was transiently decreased only at 1700 h on proestrus. Tyrosine hydroxylase mRNA levels were similar at 1000, 1330, and 1700 h on proestrus, were reduced by 50% at 2200 h on proestrus subsequent to the decrease in enzyme activity, and remained low on the morning of estrus. Okadaic acid, a protein phosphatase-1 and -2A inhibitor, induced a similar increase in tyrosine hydroxylase activity in vitro at 1330 and 2200 h on proestrus and at 1100 h on estrus, indicating that tyrosine hydroxylase was capable of being activated in spite of decreased mRNA levels. Ovariectomy between 1100-1200 h on proestrus prevented the decrease in tyrosine hydroxylase mRNA levels and in vitro DOPA accumulation at 2200 h. The effects of ovariectomy were completely reversed by progesterone, whereas estradiol had no effect. Circulating PRL levels at 2200 h were suppressed to basal levels after ovariectomy, but were increased by progesterone treatment at 1530 h to levels similar to those in the plateau phase of the PRL surge in control rats. Administration of the progesterone antagonist RU486 at 1200 h on proestrus did not alter tyrosine hydroxylase activity, tyrosine hydroxylase mRNA levels, or circulating PRL concentrations at 2200 h.(ABSTRACT TRUNCATED AT 400 WORDS)

Hormonal symphony: steroid orchestration of gene modules for sociosexual behaviors

“…With molecular probes directed to specific genes, studied primarily in female rats, several of them have been revealed as upregulated by progesterone: these include neuropeptide Y receptor, 25 34 and tyrosine hydroxylase. 35,36 The manners in which these particular downstream genes contribute to reproductive behaviors will be exciting to explore.…”

The impact of the hormonal milieu and stress-associated hypothalamic dopaminergic activation on the rapid compensatory adrenal growth in cycling female rats

“…25,39 This notion is further supported by the present results suggesting that the enhancement of short-term CAG in E after left Adx in PE is partly mediated by estrogen and progesterone-driven reduction of dopaminergic activity. In favour of this assumption are previous 32 and recent data showing that administration of estrogen to ovariectomized rats, followed by progesterone administration on the next day, decreases the dopaminergic activity in the intermediate lobe. 40 We may conclude that our present results in 4-day cycling rats indicate a profound difference of short-term IAG and CAG between PE and E. It is suggested that the expected rise in CRH, promoted by the rise of estradiol levels preceding left Adx in PE, favours the within 19-20 h significant IAG and CAG observed in E. Moreover, the expected rise in progesterone in the afternoon of PE contributes to the enhancement of CAG and IAG by reducing stress-associated dopaminergic activation.…”

“…This could be attributed, in part, to the suppression of TH mRNA levels by progesterone, as found in the arcuate nucleus in PE. 32 Recent evidence suggests that estradiol 17β may affect receptors in hypothalamic dopaminergic neurons by membrane initiated rapid signaling. 33 Thus, a possible suppressive role of estrogens through a rapid effect on dopaminergic activity cannot be excluded.…”

Differential and Interactive Effects of Ligand-Bound Progesterone Receptor A and B Isoforms on Tyrosine Hydroxylase Promoter Activity.

“…These data suggest a stimulatory action on TH gene expression through the classical nuclear PR. The inhibitory effect of progesterone is observed on the afternoon of pro-oestrus, with the initial response of decreased TH phosphorylation state in the median eminence followed by decreased TH mRNA levels in the arcuate nucleus (8)(9)(10). The stimulatory effect of progesterone on TH content is not limited to the hypothalamic neurons, as progesterone increases TH content in the olfactory bulb (11).…”

“…(1,2). These neurons express oestradiol-inducible progesterone receptor (PR) and progesterone can have both stimulatory and inhibitory actions on their activity, resulting in altered prolactin secretion (3)(4)(5)(6)(7)(8). Progesterone treatment increases tyrosine hydroxylase (TH) mRNA levels in the arcuate nucleus of oestradiol-treated ovariectomized female rats and the progesterone receptor antagonist RU486 blocks this stimulatory effect of progesterone (7).…”