2. Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
The aim of this experiment was to determine the effects of a low dose (0.2 mg/kg body weight i.v.) of the luteinizing hormone-releasing hormone (LHRH)-lytic peptide conjugate (LHRH-Phor21) on the periovulatory ovarian and endocrine events, ensuing luteal function and fertility in an ovine experimental model. We hypothesized that the dense expression of LHRH receptors on the anterior pituitary and ovarian structures would make them highly susceptible to the membrane disrupting ability of LHRH-Phor21. Six sexually mature Rideau Arcott ewes were used to test the effects of the conjugate; seven ewes served as controls. Prior to drug administration, estrus was synchronized with intravaginal medroxyprogesterone acetate (MAP)-releasing sponges that were left in place for 12 days and a single i.m. injection of 750 IU of equine chorionic gonadotropin (eCG) given at sponge removal. LHRH-Phor21 or saline were administered 36 h after MAP sponge withdrawal/eCG injection, around the expected onset of the endogenous discharge of gonadotropins. Treatment resulted in greater (p<0.05) peak LH concentrations and an earlier rise (p<0.05) in estradiol secretion in LHRH-Phor21-treated than control ewes; however, there were no differences (p>0.05) in the mean number of ultrasonographically detected luteal structures and serum progesterone concentrations during the luteal phase post-treatment. There were no differences (p>0.05) in the number of ewes that lambed or lamb characteristics between the two groups at lambing 9 months post-treatment. Overall, there was no adverse effect of LHRH-Phor21 on the ovulatory process, luteal function and lamb productivity in the ewes of the present study. With a lack of suppressive effects of LHRH-Phor21 on the pituitary-ovarian axis and fertility, our results support the suitability of the drug as a potential cancer pharmaceutical in reproductive-aged women.
Keywords: Conjugated lytic peptide, luteinizing hormone-releasing hormone, ovulation, luteogenesis, antral follicle development, ewe, transrectal ultrasonography