Inhibitory effects of a luteinizing-hormone-releasing hormone agonist implant on ovine fetal gonadotrophin secretion and pituitary sensitivity to luteinizing-hormone-releasing hormone.
Sheep fetuses at day 70 of gestation (term = 145 days) were implanted subcutaneously with a biodegradable implant containing a luteinizing-hormone-releasing hormone (LHRH) agonist (buserelin) to investigate whether treatment with LHRH agonist would induce a state of desensitization of the fetal gonadotrophs and thus influence fetal gonadal development. Treatment with the LHRH agonist for 35-40 days caused a significant reduction in mean fetal plasma concentrations of LH and follicle-stimulating hormone (FSH) compared with control fetuses. LH pulses were evident in control fetuses but were completely abolished by buserelin treatment. Furthermore, the pituitary content of LH and FSH was significantly depleted in fetuses implanted with LHRH agonist. A bolus intravenous injection of 500 ng LHRH given to control fetuses caused a rapid and significant increase in plasma LH and FSH concentrations which was sustained for at least 60 min after injection. Pretreatment with buserelin completely abolished the LH and FSH responses to a bolus injection of LHRH. There were no differences between the sexes in fetal gonadotrophin concentrations or pituitary sensitivity to LHRH in control or agonist-treated fetuses. Furthermore, buserelin treatment for 35-40 days had no effect on the morphological appearance of the fetal gonads when compared with control fetuses, at least to day 110 of pregnancy. These results provide evidence for the induction of a state of desensitization of the LHRH receptors of the fetal pituitary gonadotrophs following long-term treatment with an LHRH agonist, but provide no evidence for a role for gonadotrophin secretion in gonadal development at this stage in fetal life.
Brooks
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AN
MRC Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh, UK.
McNeilly
A S
AS
D000704:Analysis of Variance; D000818:Animals; D002064:Buserelin / Q000008:administration & dosage / Q000494:pharmacology; D004343:Drug Implants; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology*; D006062:Gonadotropins / Q000097:blood / Q000378:metabolism*; D006066:Gonads / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011863:Radioimmunoassay; D012756:Sheep / Q000196:embryology*
D004343:Drug Implants; D006062:Gonadotropins; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002064:Buserelin