Diurnal Pattern of Proopiomelanocortin Gene Expression in the Arcuate Nucleus of Proestrous, Ovariectomized, and Steroid-Treated Rats: A Possible Role in Cyclic Luteinizing Hormone Secretion

Abstract

Opiate peptides are thought to modulate the pattern of LH release in female rats. We tested the hypothesis that changes in proopiomelanocortin (POMC) gene expression occur in proestrous (PRO) and ovariectomized (OVX) steroid-treated rats which may explain their unique patterns of LH secretion. Using in situ hybridization, we examined whether diurnal changes in POMC gene expression occur in the arcuate nucleus. Four groups of rats were used in this study. 1) PRO rats were used after exhibiting at least two consecutive 4-day estrous cycles; 2) OVX rats were killed 9 days after ovariectomy; 3) estradiol (E2)-treated rats were OVX for 7 days and then treated for 2 days; and 4) E2-progesterone (P4)-treated rats were treated with E2 as described above, and on day 9 at 1030 h, P4 was administered. Rats were killed at 2300, 0300, 1000, 1300, 1500, 1800, or 2300 h, beginning on the evening of diestrous day 2 or day 8 after ovariectomy. POMC gene expression exhibited a diurnal rhythm on PRO. Levels of mRNA rose during the morning, peaked between 0300-1000 h, and decreased by 2300 h. In E2-treated rats, which exhibited a LH surge similar in timing to the PRO surge, POMC mRNA levels exhibited a diurnal rhythm strikingly similar to that observed in PRO animals. OVX abolished the rhythm; however, average POMC mRNA levels across the 24-h period were not significantly different from those in PRO or E2-treated rats. P4 treatment increased POMC mRNA levels by 2300 h compared to those in all other experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Multimodal Influence of Estrogen upon Gonadotropin-Releasing Hormone Neurons

“…In terms of the latter, it is clear that prolonged estrogen exposure decreases ␤END mRNA and peptide expression within the arcuate nucleus (380,382,383). However, ␤END peptide and mRNA analyses also show that a significant diurnal rhythm occurs within the ␤END neurons; ␤END expression is lowest in the afternoon, and this diurnal rhythm is only evident in the presence of estrogen (381,384,385). Hence, the arcuate ␤END neurons may be an additional site at which estrogen and circadian inputs are integrated before transmission to the GnRH neurons in the rat.…”

“…However, the marked increase in progesterone concentrations that follows the onset of the LH surge exerts an opposite effect to estrogen on these cells and increases ␤END mRNA levels (381,383). This is suggested to be the neural mechanism through which progesterone inhibits the occurrence of a further estrogen-induced LH surge on estrus (386,389).…”

Sex Differences in the Daily Rhythm of Vasoactive Intestinal Polypeptide But Not Arginine Vasopressin Messenger Ribonucleic Acid in the Suprachiasmatic Nuclei1

“…Animals housed under this LD cycle show a proestrous or estrogen-induced surge of LH between 1500 -1800 h (33). Estrous cyclicity was monitored using vaginal cytology.…”

“…Sections were thaw mounted onto slides and stored at Ϫ70 C until they were processed for in situ hybridization following a previously established protocol (33). A total of 52 sections (26 slides) containing the SCN were collected from each animal.…”

Decrease of the Number of Opioid Receptors and of the Responsiveness to Morphineduring Neuronal Differentiation Induced by 17β-Estradiol in Estrogen Receptor-Transfected Neuroblastoma Cells (SK-ER3)

“…For instance, estrogens may modify the production and the release of endogenous opioids [5], as well as the binding characteristics of brain opioid receptors [6]. Findings from this and other laboratories have shown that, in female rats, the phyisological fluctuations of estrogens and progesterone during the estrous cycle, as well as during pregnancy, are accompanied by modifications of the concentration of µ opioid receptors in the brain [7, 8, 9, 10].…”