Gonadal steroid hormone regulation of hypothalamic opioid function

Abstract

β-Endorphin- (β-Endo) like immunoreactive (IR) fibers in the medial preoptic area (MPOA) have been shown to vary in density across the estrous cycle. The proopiomelanocortin (POMC) neurons which produce this innervation of the MPOA are located in the arcuate nucleus (ARC). The POMC mRNA level in the ARC neurons also varies across the estrous cycle. However, the effects of gonadal steroid hormones on the distribution and density of β-endo-like IR fibers in the MPOA, and on the regulation of POMC gene expression in ARC neurons which project to the MPOA of ovariectomized (OVX) female rats are unclear. In the present studies, immunohistochemical staining, and combined fluorogold (FG) retrograde labeling and in situ hybridization histochemistry were used to investigate these unknown problems. In the MPOA, the density of β-endo-like IR fibers was low in OVX animals, increased slightly following 17β-estradiol (E2) treatment or 3 hr after progesterone (P) injection. However, β-endo-like IR fiber density increased remarkably 27 hr after E2P treatment, and remained elevated 51 hr after E2P treatment POMC mRNA expression was low in ARC neurons of OVX animals, significantly increased in the rostral ARC 48 hr after E2 treatment, and P administration enhanced the E2 effect in rostral ARC neurons. In the other ARC regions, E2P significantly increased POMC mRNA beginning 13 hr after P injection. E2P treatment did not produce more POMC-containing fibers to innervate the MPOA. These results suggest that the density of MPOA β-endo-like IR fibers is gonadal steroid hormone-dependent, but the pattern of innervation of the MPOA by POMC neurons is unaffected by gonadal steroid hormone treatment. Gonadal steroid hormones appear to activate POMC expression in ARC neurons, stimulate the synthesis of β-endo in POMC neurons which project to the MPOA, and eventually promote transport of β-endo from POMC neurons in the ARC to the β-endo-containing axons in the MPOA. That steroid hormones functionally affect ARCPOMC mRNA expression and MPOA B-endo density implicates the roles of this endogenous opioid in regulating hormonal cyclicity and reproductive behavior.