Polypeptides Antagonists of the Hypothalamic Luteinizing Hormone Releasing Factor

Abstract

Techniques are described for the solid-phase synthesis of the decapeptide luteinizing hormone releasing factor (LRF) and for the testing of its biological activity in vitro (dispersed cells of rat pituitary gland in monolayer cultures). The biological activity of several (LH)LRF analogues is reported. Two analogues of the hypothalamic Luteinizing hormone releasingthalamic modified factor at the histidine-2 position were tested for biological activity (secretion of luteinizing hormone) in cultures of dis- persed rat anterior pituitary cells. The analogue in which glycine was substituted for histidine at position-2 [Gly²] LRF behaves as a partial agonist releasing less than 50 % of the luteinizing hormone secreted at maximum concentrations of the releasing factor, while the analogue in which histidine at position-2 is deleted has no significant agonist activity at any of the doses tested. When added to the cultured cells at molar ratios 103 to 101 times that of the luteinizing hormone releasing factor, both analogues decrease the amount of luteinizing hormone secreted in response to the releasing factor.

O Ρόλος Ωοθηκικών Παραγόντων Στην Έκκριση Των Γοναδοτροφινών Της Υπόφυσης

“…Το 1971, το μικρό δεκαπεπτίδιο GnRH απομονώθηκε, και η δομή του διευκρινίστηκε (Guillemin et al 1971, Schally et al 1971. Πειραματικές δοκιμασίες με αντικαταστάσεις αμινοπεπτιδίων αποκάλυψαν τη σημασία συγκεκριμένων περιοχών για τη σταθερότητα του, την ικανότητα σύνδεσης με υποδοχείς και την διέγερση υποφυσιακών κυττάρων για έκκριση γοναδοτροφινών (Schally 1999).…”