Control of LH secretion in red deer (Cervus elaphus)

Abstract

The feedback effects of ovarian steroids on the secretion of luteinizing hormone (LH) have been well established in many species. This thesis describes a series of studies which examined the effects of oestradiol, progesterone, and season on the pulsatile secretion of LH in red deer (Cervus elaphus). In the first experiment two groups of long-term ovariectomized hinds (n=10, with and without intravaginal progesterone pre-treatment) were injected i.m. with 0, 5, or 100 µg oestradiol-17β, 24 h after the withdrawal of progesterone treatment. Eight entire hinds were included in these experiments as a control group (endogenous oestradiol). LH concentration was measured in plasma samples taken at regular intervals for up to 38 h in the anoestrous (February and March, 1990) and breeding seasons (April and May, 1990). In ovariectomized hinds, a low dose of oestradiol (5 µg) was able to suppress LH pulse frequency and mean concentration in the anoestrous season, but not in the breeding season. Dosage of oestradiol affected the time to onset of suppression - the greater the dose, the shorter the time required, and the high dose (100 µg) elicited a biphasic response of LH secretion. The latter response was an initial suppression (negative feedback) followed by an increase in LH pulse frequency (positive feedback) which culminated in a preovulatory LH surge-like secretion pattern 16.7 ± 2.9 h after oestradiol injection. LH surges were also evident in entire hinds after the withdrawal of progesterone pre-treatment and the timing of these surges and their characteristics were comparable to those of ovariectomized hinds. Progesterone exhibited two roles in the regulation of secretion of LH, namely an inhibitory effect on LH secretion during its presence and a priming effect on the subsequent LH secretory response to the stimulatory effect of oestradiol. Moreover, the decline of plasma progesterone concentration (following the withdrawal of intravaginal progesterone treatment) advanced the timing of onset of LH surges.

The second experiment was carried out to define the site where oestradiol achieved its negative feedback effect. Exogenous GnRH (50 ng/kg live weight) was injected i.v. into ovariectomized hinds (n=9) 8 h following injection of 0, 5, or 100 µg oestradiol. All hinds had an elevation of plasma LH concentration immediately after injection of GnRH, indicating that the pituitary was responsive to GnRH even when LH secretion was suppressed by oestradiol. However, the amplitude of the LH response was lower in oestradiol-treated hinds than in control animals, suggesting that pituitary responsiveness to GnRH was partly suppressed by oestradiol treatment. This indicated that in red deer hinds oestradiol achieved its negative feedback effects at both hypothalamic and pituitary gland sites.

Another study investigated the effect of dose of exogenous GnRH on LH pulse amplitude. Four anoestrous hinds were injected with 0, 2, 4, and 16 µg GnRH so that each hind received every dose, 1 dose per day over 4 days. The results showed a direct relationship between dose of GnRH and amplitude of the LH response. Therefore, in red deer LH pulse amplitude is partly governed by GnRH pulse amplitude.

Sexual differences in the feedback effects of oestradiol on LH secretion were investigated by carrying out a study, comparable to the first experiments, on long-term castrated stags (n=6). These were conducted in December 1990 (non-breeding season) and May 1991 (breeding season). LH pulse frequency in these stags was suppressed by oestradiol treatment but only at the higher dose (100 µg) and there was no evidence of change in pituitary responsiveness to the injection of exogenous GnRH (50 ng/kg live weight). This indicated that, although oestradiol had a negative feedback effect on LH secretion in stags as well as in hinds, there were some sexual differences in the regulation of secretion of LH in red deer. These included lower sensitivity of stags to the inhibitory effects of oestradiol and an evidence that oestradiol exerted its effect at the level of the hypothalamus only.

These studies also showed that the seasonal shifts in LH secretion of red deer were due to alteration in sensitivity to the inhibitory feedback effect of oestradiol and also to a direct steroid-independent effect of season on the hypothalamo-pituitary axis.

The experiments described in this thesis have added to the fundamental knowledge of the interrelationship between components of the hypothalamo-pituitary-axis in red deer and are the first to examine collectively the effects of oestradiol, progesterone, season and sex in this species. They have shown that the interaction between the feedback effects of oestradiol and the secretion of LH in red deer is similar to that which is well established in sheep.