1. Ultrashort feedback control of luteinizing hormone-releasing hormone secretion in vitro
M Zanisi, M Motta, L Martini, E Messi Endocrinology . 1987 Dec;121(6):2199-204. doi: 10.1210/endo-121-6-2199.
The present experiments were performed to clarify whether LHRH might inhibit its own secretion via an ultrashort feedback mechanism acting directly on the hypothalamus. Using an in vitro system, mediobasal hypothalami (MBHs) of adult male rats were perifused in either the presence or absence of a LHRH agonistic analog [D-Ser(TBU)6,Des-Gly10] LHRH ethylamide shown not to cross-react in the LHRH RIA. In the first series of experiments, six MBHs per chamber were initially perifused with control medium and submitted to two K+ stimulations (110 mM) for 5 min every 30 min; the control medium was then replaced by medium containing the LHRH analog (5 microM), and three additional K+ pulses were applied. In the second series of experiments, a single MBH per chamber was exposed for the duration of the experiments to either control medium or medium containing the LHRH analog (5 microM). In both cases, pulses of K+ were applied to the tissue. The amounts of endogenous LHRH released both under basal conditions and after K+ stimulation were measured in the effluent (1 ml every 5 min) with a specific RIA. The results show that the LHRH analog inhibits basal secretion of endogenous LHRH from the MBH, and diminishes or abolishes the response to K+ stimulations. The specificity of the inhibitory effect exerted by the LHRH analog on LHRH secretion was shown by the inability of TRH to mimic the effect of the LHRH analog. The data are consistent with the hypothesis that LHRH, acting at a hypothalamic level, might participate in the control of its own release via an ultrashort feedback mechanism.
2. Effect of pre-treatment of long-term ovariectomized rats with anti-LRH on the response of the pituitary gland in vitro to the analogue of LRH D-ser-(tBu)6-des-gly10-ethylamide-LRH (Buserelin)
J de Koning, G P van Rees, J A van Dieten, A F de Goey Acta Endocrinol (Copenh) . 1983 Nov;104(3):272-8. doi: 10.1530/acta.0.1040272.
Ovariectomized rats were injected iv with an antiserum against LRH or normal rabbit serum. Anti-LRH caused a decrease of plasma LH and FSH. After 24 or 48 h, the rats were decapitated and the pituitary glands incubated in the presence of an analogue of LRH which reacts minimally with anti-LRH (Buserelin). Pre-treatment with anti-LRH caused an increased response of pituitary LH release to Buserelin. Similar results were obtained with regard to FSH. In this case, however, basal release of FSH was lowered by pre-treatment with anti-LRH. Pituitary LH and FSH contents were not affected by anti-LRH, but synthesis of LH and FSH in vitro was smaller than in control glands obtained from rats pre-treated with normal rabbit serum.
3. The pituitary-gonadal response to the gonadotrophin releasing hormone analogue D-Ser (TBU)6-Des Gly10-LHRH-ethylamide in normal men
F Mulligan, B Mora, M J Watson, M H Snow, M F Scanlon, M Heath, R Hall, A Gomez-Pan Clin Endocrinol (Oxf) . 1979 Mar;10(3):297-303. doi: 10.1111/j.1365-2265.1979.tb02084.x.
We have studied the dose-response characteristics of the LHRH analogue D-Ser (TBU)6-Des Gly10-LHRH-ethylamide administered subcutaneously to five normal male volunteers. The relative potency of the analogue is about sixty times (FSH) and forty times (LH) that of the parent peptide and the increased potency and duration of action of the analogue lead to enhanced biological effect in terms of testosterone release. The prolonged duration of action of the analogue suggests that a single daily dosage regime could be used although further chronic studies with this potent analogue should be undertaken in normal volunteers to determine optimum dosage schedules.
