Activation of cells containing estrogen receptor alpha or somatostatin in the medial preoptic area, arcuate nucleus, and ventromedial nucleus of intact ewes during the follicular phase, and alteration after lipopolysaccharide

Abstract

Cells in the medial preoptic area (mPOA), arcuate nucleus (ARC), and ventromedial nucleus (VMN) that possess estrogen receptor alpha (ER alpha) mediate estradiol feedback to regulate endocrine and behavioral events during the estrous cycle. A percentage of ER alpha cells located in the ARC and VMN express somatostatin (SST) and are activated in response to estradiol. The aims of the present study were to investigate the location of c-Fos, a marker for activation, in cells containing ER alpha or SST at various times during the follicular phase and to determine whether lipopolysaccharide (LPS) administration, which leads to disruption of the luteinizing hormone (LH) surge, is accompanied by altered ER alpha and/or SST activation patterns. Follicular phases were synchronized with progesterone vaginal pessaries, and control animals were killed at 0, 16, 31, and 40 h (n = 4-6/group) after progesterone withdrawal (PW [time 0]). At 28 h, other animals received LPS (100 ng/kg) and were subsequently killed at 31 h or 40 h (n = 5/group). Hypothalamic sections were immunostained for c-Fos and ER alpha or SST. LH surges occurred only in control ewes with onset at 36.7 ± 1.3 h after PW; these animals had a marked increase in the percentage of ER alpha cells that colocalized c-Fos (%ER alpha/c-Fos) in the ARC and mPOA from 31 h after PW and throughout the LH surge. In the VMN, %ER alpha/c-Fos was higher in animals that expressed sexual behavior than in those that did not. SST cell activation in the ARC and VMN was greater during the LH surge than in other stages in the follicular phase. At 31 or 40 h after PW (i.e., 3 or 12 h after treatment, respectively), LPS decreased %ER alpha/c-Fos in the ARC and the mPOA, but there was no change in the VMN compared to that in controls. The %SST/c-Fos increased in the VMN at 31 h after PW (i.e., 3 h after LPS) with no change in the ARC compared to controls. These results indicate that there is a distinct temporal pattern of ER alpha cell activation in the hypothalamus during the follicular phase, which begins in the ARC and mPOA at least 6-7 h before the LH surge onset and extends to the VMN after the onset of sexual behavior and LH surge. Furthermore, during the surge, some of these ER alpha-activated cells may be SST-secreting cells. This pattern is markedly altered by LPS administered during the late follicular phase, indicating that the disruptive effects of this stressor are mediated by suppressing ER alpha cell activation at the level of the mPOA and ARC and enhancing SST cell activation in the VMN, leading to the attenuation of the LH surge.

Keywords: LH surge; LPS; estrogen receptor alpha; ewes; sexual behavior; somatostatin; stress.