Endogenous Opioid Suppression of Luteinizing Hormone Pulse Frequency and Amplitude in the Ewe: Hypothalamic Sites of Action

Abstract

Evidence suggests that endogenous opioid peptides (EOP) inhibit pulsatile luteinizing hormone (LH) secretion during both the luteal and follicular phases of the ovine estrous cycle. Further data from sheep and other species indicate that the hypothalamus is the primary site of action for this EOP inhibition. The purpose of the following experiments was to determine which areas of the hypothalamus are involved in the EOP inhibition of pulsatile LH secretion. Regularly cycling ewes (n = 10) were stereotaxically implanted with guide tubes into the preoptic area (POA) and medial basal hypothalamus (MBH). Implants containing the EOP antagonist WIN 44,441–3 (WIN) were placed into each of these areas. Blood samples were collected at 12-min intervals for 3 h before and during WIN administration in the luteal phase and for 4 h before and during WIN administration in the follicular phase of the estrous cycle. During the luteal phase, WIN implants in either area increased (p < 0.01) LH pulse frequency (POA 1.4 ± 0.3/3 h before vs. 3.1 ± 0.4/3 h during; MBH 1.1 ± 0.2/3 h before vs. 2.8 ± 0.5/3 h during). There was no effect on LH pulse amplitude. In contrast, during the follicular phase, WIN implants selectively increased (p < 0.01) LH pulse frequency when implanted in the POA (3.2 ± 0.4/4 h before vs. 5.2 ± 0.6/4 h during) while increasing (p < 0.05) only LH pulse amplitude when placed in the MBH (0.7 ± 0.2 ng/ml before vs. 1.4 ± 0.3 ng/ml during). These results suggest that although EOP act in both POA and MBH to inhibit LH secretion, different populations of EOP neurons may be activated during different phases of the estrous cycle.

Blockade of the Oestrogen-Induced Luteinizing Hormone Surge in Ovariectomized Ewes by a Highly Selective Opioid µ-Receptor Agonist: Evidence for Site of Action

“…The data are, however, consistent with such a hypothesis, and consistent with the evidence for dual sites of opioid regulation of GnRH secretion in the luteal and follicular phases of the oestrous cycle [14, 15, 16, 17]. …”

“…Infusion of β-endorphin antiserum into MPOA, but not MBH, increased plasma LH levels, whereas met-enkephalin antiserum had the same effect when infused into MBH or anterior hypothalamic area, but not MPOA [16]. In luteal phase ewes, the opiate antagonist WIN 44,441-3 (WIN) increased LH pulse frequency when implanted into either POA or MBH [14]. WIN implants in the POA also increased LH pulse frequency in the follicular phase of the oestrous cycle, whereas implants in the MBH increased LH pulse amplitude but not frequency [14].…”

“…In luteal phase ewes, the opiate antagonist WIN 44,441-3 (WIN) increased LH pulse frequency when implanted into either POA or MBH [14]. WIN implants in the POA also increased LH pulse frequency in the follicular phase of the oestrous cycle, whereas implants in the MBH increased LH pulse amplitude but not frequency [14]. Finally, during both the follicular and luteal phases of the cycle, naloxone administration into the ME through a push-pull perfusion cannula increased GnRH concentrations in push-pull perfusates, whereas β-endorphin infusion by the same route reduced GnRH levels in the perfusate [15].…”

“…Previous studies have shown that infusion of opiate antagonists into either the MPOA or the mediobasal hypothalamus (MBH), close to the ME, can increase GnRH and LH secretion in sheep during the luteal and follicular phases of the oestrus cycle [14, 15, 16, 17]. This suggests that there may be dual sites of opioidergic regulation of GnRH secretion.…”

Ovarian function in ewes made hypogonadal with GnRH antagonist and stimulated with FSH in the presence or absence of low amplitude LH pulses

“…Group 1 (n=8) were treated with FSH (5 µg/h) for 3 days without LH and Group 2 (n=10) were treated with FSH (5 µg/h) for 3 days with LH (2·5 µg administered as a bolus injection every 4 h). This dose of LH has been shown to induce an LH pulse of similar magnitude to that observed during a normal luteal phase (Baird et al 1976, Wallace & McNeilly 1986, Whisnant et al 1991. Ovarian (5 ml) and jugular (3 ml) venous blood samples were taken every 4 h over the experimental period and there were three periods of intensive blood sampling 24, 48 and 72 h after the start of FSH infusion.…”