Effect of stress-like concentrations of cortisol on the feedback potency of oestradiol in orchidectomized sheep

The effect of stress-like concentrations of cortisol on oestradiol-induced change in LH secretion and GnRH receptor expression was evaluated in orchid ectomized sheep (wethers). Twenty-four wethers were assigned at random to o ne of the four treatment groups in a 2 x 2 factorial design (n = 6 wethers/ group). Wet hers received cortisol (90 mu g/kg/h; groups 2 and 4) or a comp arable volume of cortisol delivery vehicle (groups 1 and 3) by continuous i nfusion for 48 h, During the final 24 h of infusion, wethers received oestr adiol (6 ng/kg/h; groups 3 and 4) or oestradiol delivery vehicle (groups 1 and ?). The pattern of LH secretion was assessed during a 3-h period of int ensive blood collection beginning 21 h after initiation of oestradiol infus ion. Although neither cortisol nor oestradiol alone affected (P > 0.05) mea n serum concentration of LII or LH pulse frequency, serum LW and the freque ncy of secretory episodes of LH were significantly reduced (P < 0.05) in we thers receiving cortisol and oestradiol in combination. Anterior pituitary tissue was collected at the end of the infusion period. Oestradiol increase d (P < 0.05) tissue concentrations of GnRH receptor and GnRH receptor mRNA. Although cortisol alone did not affect(P > 0.05) basal concentrations of r eceptor or receptor mRNA, the magnitude of oestradiol-induced increase in G nRH receptor and GnRH receptor mRNA was significantly reduced in wethers re ceiving cortisol and oestradiol concurrently. Conversely, steady-state conc entrations of mRNA encoding the LH beta and FSH beta subunits were increase d (P < 0.05) in wethers receiving cortisol. These observations demonstrate that stress-like concentrations of cortisol act in concert with oestradiol to suppress LII secretion. In addition, cortisol blocks oestradiol-dependen t increase in pituitary tissue concentrations of GnRH receptor and GnRH rec eptor mRNA. (C) 2000 Elsevier Science B.V. All rights reserved.