H Sakurai

Effect of duration of infusion of stress-like concentrations of cortisol on follicular development and the preovulatory surge of LH in sheep.

Stress-like levels of cortisol suppress follicular growth and development and block or delay the preovulatory surge of LH when cortisol is continuously administered during the late luteal and early follicular phases of the ovine oestrous cycle. We postulated that cortisol infusion of shorter duration would have a similar effect. To test this hypothesis the oestrous cycles of mature ewes were synchronized using progestin-treated vaginal pessaries. Ewes were randomly assigned to one of four treatment groups. Animals received cortisol (0.1mg/kg/h; n=8) or vehicle alone (n=8) beginning 5 days before, and continuing for 5 days after, pessary removal (PR). Additional groups received cortisol only during the 5 days period before (n=7), or the 5 days period after (n=8), PR. Continuous delivery of cortisol established stable serum concentrations of cortisol of 72.0+/-2.5ng/ml within 6h of initiation of infusion. Serum concentrations of oestradiol increased progressively during the period after PR in control animals receiving vehicle alone and the preovulatory surge of LH was evident in all control animals (eight of eight) 55.5+/-5.0h after PR. In contrast, follicular development and the preovulatory surge of LH were evident during the period of cortisol infusion in only one of eight animals receiving stress-like levels of cortisol over the entire 10-day infusion period. Similarly, neither follicular development nor surge-like secretion of LH were evident during the infusion period in animals (zero of eight) receiving cortisol during the 5-day period after PR. This cortisol-dependent suppression of ovarian activity in sheep receiving stress-like levels of cortisol during the 5 days after PR was temporary and follicular development, the ovulatory surge of LH, and subsequent luteal function were evident in six of eight ewes after cessation of cortisol delivery. Similarly, follicular development and the preovulatory surge of LH were noted within 5 days after PR in four of seven ewes receiving cortisol only during the 5-day period prior to PR. Collectively, these data indicate that stress-like levels of cortisol reduce fertility of sheep by suppressing follicular development and the preovulatory surge of LH. Additionally, cortisol delivery during the follicular phase has a more profound suppressive effect on follicular development than cortisol administration during the luteal phase.

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 orchidectomized sheep (wethers). Twenty-four wethers were assigned at random to one of the four treatment groups in a 2x2 factorial design (n=6 wethers/group). Wethers received cortisol (90 microg/kg/h; groups 2 and 4) or a comparable volume of cortisol delivery vehicle (groups 1 and 3) by continuous infusion for 48 h. During the final 24 h of infusion, wethers received oestradiol (6 ng/kg/h; groups 3 and 4) or oestradiol delivery vehicle (groups 1 and 2). The pattern of LH secretion was assessed during a 3-h period of intensive blood collection beginning 21 h after initiation of oestradiol infusion. Although neither cortisol nor oestradiol alone affected (P>0.05) mean serum concentration of LH or LH pulse frequency, serum LH and the frequency of secretory episodes of LH were significantly reduced (P<0.05) in wethers receiving cortisol and oestradiol in combination. Anterior pituitary tissue was collected at the end of the infusion period. Oestradiol increased (P<0.05) tissue concentrations of GnRH receptor and GnRH receptor mRNA. Although cortisol alone did not affect (P>0.05) basal concentrations of receptor or receptor mRNA, the magnitude of oestradiol-induced increase in GnRH receptor and GnRH receptor mRNA was significantly reduced in wethers receiving cortisol and oestradiol concurrently. Conversely, steady-state concentrations of mRNA encoding the LHbeta and FSHbeta subunits were increased (P<0.05) in wethers receiving cortisol. These observations demonstrate that stress-like concentrations of cortisol act in concert with oestradiol to suppress LH secretion. In addition, cortisol blocks oestradiol-dependent increase in pituitary tissue concentrations of GnRH receptor and GnRH receptor mRNA.