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 follicular development and the preovulatory surge of LH in sheep.

Stress-like concentrations of cortisol increase the negative feedback potency of oestradiol in castrated male sheep. A similar cortisol-dependent response in female sheep might be expected to suppress gonadotrophin secretion and impair follicular development and ovulation. The oestrous activity of 21 female sheep was synchronized using progestogen-treated vaginal pessaries to test this hypothesis. Stress-like concentrations of cortisol (60-70 ng ml-1) were established by continuous infusion of cortisol (80 micrograms kg-1 h-1; n = 13) beginning 5 days before, and continuing for 5 days after, pessary removal. Control animals (n = 8) received a comparable volume of vehicle (50% ethanol-saline) over the 10 day infusion period. Serum concentrations of oestradiol increased progressively in control sheep during the 48 h immediately after pessary removal. This increase in serum oestradiol was blocked or significantly attenuated in sheep receiving stress-like concentrations of cortisol. Preovulatory surge-like secretion of LH was apparent in control animals 58.5 +/- 2.1 h after pessary removal. In contrast, surge-like secretion of LH was not observed during the 5 days after pessary removal in 54% (7 of 13) of sheep receiving cortisol. Moreover, the onset of the surge was significantly delayed in the cortisol-treated ewes that showed surge-like secretion of LH during the infusion period. The ability of episodic pulses of exogenous GnRH to override the anti-gonadal effect of cortisol was examined in a second study. Oestrous activity of 12 ewes was synchronized using progestogen-containing pessaries as described above. Ewes were randomly assigned to one of three treatment groups (n = 4 ewes per group). Animals received cortisol (100 micrograms kg-1 h-1; groups 1 and 2) or a comparable volume of vehicle (group 3) beginning 5 days before, and continuing for 2 days after, pessary removal. Pulses of GnRH (4 ng kg-1 h-1, i.v.; group 1) or saline (groups 2 and 3) at 1 h intervals were initiated at pessary removal and continued for 48 h. Serum concentrations of oestradiol were not significantly increased after pessary removal in sheep receiving cortisol alone. Conversely, serum concentrations of oestradiol increased progressively during the 48 h after pessary removal in control ewes and in ewes receiving cortisol and GnRH. At the end of infusion, serum concentrations of oestradiol did not differ (P > 0.05) between control (7.7 +/- 0.8 pg ml-1) ewes and ewes receiving cortisol and episodic GnRH (6.4 +/- 1.3 pg ml-1). Moreover, these values were significantly greater (P < 0.05) than the serum concentrations of oestradiol in animals receiving cortisol (1.0 +/- 0.4 pg ml-1) alone. Collectively, these data indicate stress-like concentrations of cortisol block or delay follicular development and the preovulatory surge of LH in sheep. In addition, episodic GnRH overrides cortisol-induced delay in follicular maturation.