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Volume 16, Number 9, Issue of May 1, 1996 pp. 3035-3044
Copyright ©1996 Society for Neuroscience

Hormonal Regulation of CREB Phosphorylation in the Anteroventral Periventricular Nucleus

Received Nov. 6, 1995; revised Feb. 6, 1996; accepted Feb. 9, 1996.

Guibao Gu¹, Anthony A. Rojo¹, Michele C. Zee¹, Jianhua Yu¹, and Richard B. Simerly^{1, 2}

¹ Division of Neuroscience, Oregon Regional Primate Research Center, Beaverton, Oregon 97006, and ² Program in Neuroscience, Oregon Health Sciences University, Portland, Oregon 97201

The anteroventral periventricular nucleus (AVPV) is a nodal point in neural circuits regulating secretion of gonadotropin and contains sexually dimorphic populations of hormonally regulated dopamine-, dynorphin-, and enkephalin-containing neurons. Because the tyrosine hydroxylase (TH), prodynorphin (PDYN), and proenkephalin (PENK) genes contain cAMP response elements that control their expression in their promoters, we used histochemical methods to determine whether ovarian steroids alter expression of the cAMP response element-binding protein (CREB) in the AVPV. Because the ability of CREB to activate transcription depends on phosphorylation at Ser¹³³, we also evaluated the effects of acute steroid treatment on levels of phosphorylated CREB (pCREB) in AVPV neurons by using an antibody that differentiates between CREB and pCREB. Treatment of ovariectomized rats with estradiol treatments caused a significant induction in the number of pCREB-immunoreactive nuclei within 30 min that was maintained for at least 4 hr, but did not alter CREB immunostaining in the AVPV. Pretreatment with the estrogen antagonist Nafoxidine blocked this induction. In contrast, acute administration of progesterone to estrogen-primed animals suppressed and then increased pCREB staining in the AVPV at 30 and 60 min, respectively; no significant differences between experimental and control animals were apparent by 2 hr after progesterone treatment. Double-labeling experiments showed that pCREB was colocalized with PDYN, PENK, or TH mRNA in the AVPV, suggesting that pCREB may mediate the effect of steroid hormones on gene expression in these neurons.

Key words: anteroventral periventricular nucleus; preoptic region; cAMP response element-binding protein; immunohistochemistry; ovarian steroids; estrogen; progesterone

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