Active Immunization of Intact Mares against Gonadotropin-Releasing Hormone: Differential Effects on Secretion of Luteinizing Hormone and Follicle-Stimulating Hormone

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Abstract
Five lighthorse mares were actively immunized against gonadotropin releasing hormone (GnRH) to determine the relative importance of this hypothalamic hormone in the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Five mares immunized against the conjugation protein served as controls. Mares were initially immunized in November and received secondary immunizations 4 wk later, and then at 6-wk intervals until ovariectomy in June. All mares immunized against GnRH exhibited an increase (p<0.01) in the binding of tritiated GnRH by plasma, an indication that antibodies against this hormone had been elicited. Concentrations of LH, FSH and progesterone in weekly blood samples were lower (p<0.05) in GnRH-immunized mares than in controls after approximately 4 mo of immunization. However, the LH concentrations were affected to a greater degree than were FSH concentrations. All five control mares exhibited normal cycles of estrus and diestrus in spring, whereas no GnRH-immunized mare exhibited cyclic displays of estrus up to ovariectomy. All mares were injected intravenously with a GnRH analog (which cross-reacted < 0.1% with the anti-GnRH antibodies) in May, after all control mares had displayed normal estrous cycles, to characterize the response of LH and FSH in these mares; two days later, the mares were injected with GnRH. The LH response to the analog, which was assessed by net area under the curve, was lower (p<0.01) by approximately 99% in mares immunized against GnRH than in control mares. In contrast, the FSH response to the analog was similar for both groups. The FSH response to GnRH in mares immunized against GnRH was 85% lower than that in control mares (p<0.05), an indication that the antibodies against GnRH did prevent much of the injected GnRH from reaching the pituitary. At ovariectomy, combined ovarian weights of GnRH-immunized mares were 57% lower than those of control mares (p<0.01); numbers offollicles and corpora lutea were also lower (p<0.O1) than those of controls. It was concluded that LHand to some degree FSH secretion, and probably LHproduction, in the mare are dependent upon the bioavailability of GnRH. However, the lack of effect of GnRH-immunization on FSH response to the analog indicates that FSH stores in the pituitary (and perhaps FSH production) are relatively independent of GnRH bioavailability.

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