Effects of Chronic LHRH Treatment on Brain LHRH Content, Pituitary and Plasma LH and Ovarian Follicular Activity in the Anestrous Ewe1

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Abstract
Nine mature, anestrous ewes were used in the experiment. Osmotic minipumps (Alza Corp.) containing 1.7 mg synthetic LHRH [luteinizing hormone releasing hormone] in 170 .mu.l saline were implanted s.c. into 4 sheep. Each ewe received 4 minipumps, implanted 1 wk apart. This treatment resulted in a relatively uniform level (54 .+-. 2 pg/ml, .hivin.X .+-. standard error of the mean) of LHRH-like immunoreactivity in plasma during the 4 wk period. After 4 wk, the sheep were killed and the stalk-median eminence (SME), hypothalamus proper (HP), preoptic-suprachiasmatic area (PO-SC), a sample of cerebral cortex (C) and the pineal gland (PG) were removed from the brain, homogenized in acidified ethanol and assayed for LHRH. Chronic exposure to LHRH was without effect on the contents of LHRH in the SME, HP or PO-SC, which were 50 .+-. 5, 5.1 .+-. 0.6 and 4.8 .+-. 0.8 ng, respectievely. LHRH was not detected in C. LHRH treatment did increase the content of LHRH in the PG (treated = 125 .+-. 24 pg, control = 80 .+-. 12 pg, P < 0.05). The midventral brain regions of the anestrous ewe do not take up or retain detectable amounts of exogenous LHRH. In contrast, the PG has this ability. Each ewe responded to the initial minipump implantation with a rapid release of LH, reaching peak levels (110 .+-. 30 ng/ml) 3 h postimplantation, after which LH levels remained above those of control ewes for 24 h. There was also a release of LH following the 2nd wk implantation, but compared to the first it was less in magnitude and duration. Basal LH levels were measured during the remainder of the experiment. Continuous administration of LHRH for 4 wk reduced the content of LH in the anterior pituitary by 95% (P < 0.001). In 3 of the 4 LHRH treated ewes, plasma progesterone levels increased and remained elevated for 12 days, indicative of postovulatory luteal function. Treatment reduced the number of ovarian follicles > 2 mm in diameter (P < 0.01). The initial response of LH to the sustained administration of LHRH appears to be sufficient to induce ovulation and subsequent luteal function. The long term response, however, is not adequate to maintain ovarian follicular development.