Gonadal Steroid Hormone Regulation of Proopiomelanocortin Gene Expression in Arcuate Neurons That Innervate the Medial Preoptic Area of the Rat

Abstract

The density of beta-endorphin (beta-endo)-like immunoreactive (IR) fibers in the medial preoptic area (MPOA) has been shown to vary across the estrous cycle and is gonadal steroid hormone-dependent. These beta-endo-containing fibers are presumably projections of proopiomelanocortin (POMC) neurons which are located in the arcuate nucleus (ARC). POMC mRNA level varies across the estrous cycle in the ARC and its expression is differentially altered by gonadal steroid hormones. However, it is unclear how gonadal steroids regulate POMC gene expression in ARC neurons that innervate the MPOA. Therefore, combined fluorogold (FG) retrograde neuronal labeling and in situ hybridization histochemistry were used to investigate the effects of gonadal steroid hormone treatment on POMC gene expression in ARC neurons supplying the MPOA of ovariectomized (OVX) female rats. POMC-expressing cells were located in the ARC and median eminence (ME), wherein such neurons were significantly larger than unlabeled cells that surround them. A relatively greater number of ARC POMC neurons were observed to innervate the medial portion of the medial preoptic nucleus (MPN) than the lateral portion of the MPN. Estradiol (E2) and progesterone (P) treatment before FG injection did not affect the number of FG and POMC double-labeled neurons in the ARC, which suggests that hormone treatment did not alter the number of POMC-expressing neurons projecting to the MPN. In OVX animals, ARC POMC mRNA labeling was relatively low, and increased significantly in neurons of the most rostral ARC region 48 h after E2 treatment. P administration enhanced and prolonged the effect of E2 in this group of ARC neurons. E2P treatment significantly increased POMC mRNA expression beginning 13 h after P injection in all but the most caudal ARC POMC neurons. Thereafter, E2P treatment gradually increased POMC mRNA expression for at least 1 additional day. Gonadal steroid hormone treatment apparently affects POMC mRNA expression uniformly in neurons of the same ARC subdivision without regard to their efferent targets. Diurnal variation of POMC mRNA expression is present only in the most rostral ARC region, which contains a population of E2-sensitive POMC neurons. The results suggest that the relatively greater beta-endo-like IR fiber density in the medial MPN is due to a greater number of POMC neurons innervating this region. The pattern of innervation of the MPN by POMC neurons is unaffected by gonadal steroid hormone treatment, which appears to induce POMC expression in ARC neurons, and eventually to stimulate the synthesis and transport of beta-endo in POMC neuronal axons which project to the MPOA.(ABSTRACT TRUNCATED AT 400 WORDS)