Desensitization studies using perifused rat pituitary cells show that growth hormone-releasing hormone and His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 stimulate growth hormone release through distinct receptor sites.
The hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) and GH-releasing factor (GHRH) produced a rapid release of GH upon perifusion of dispersed rat pituitary cells. In contrast to the native hormone GHRH, GHRP-6 elicited a response of short duration. When perifusion of each secretagogue was continued until the cells no longer released GH, a challenge by the alternative secretagogue immediately resulted in a secondary release of GH. These results are consistent with each secretagogue causing desensitization of discrete receptor-linked second messenger pathways. Cells which were perifused for 1 min with GHRP-6 required continued perifusion with culture medium alone for 60 min before they completely regained responsiveness to a subsequent challenge with GHRP-6. Somatostatin (SRIF) was able to inhibit the action of either secretagogue completely. However, when both GHRH and GHRP-6 were perifused together, SRIF attenuated but did not block GH secretion. These perifusion data add support to conclusions derived from static cell culture studies, that GHRH and GHRP-6 act through different receptor sites and that through discrete signalling pathways their individual effects on GH release are amplified.
Merck Sharp & Dohme Research Laboratories, Department of Growth Biochemistry and Physiology, Rahway, New Jersey 07065.
A D
AD
Blake
R G
RG
Smith
D000818:Animals; D002478:Cells, Cultured; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010477:Perfusion; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015290:Second Messenger Systems / Q000502:physiology; D013004:Somatostatin / Q000494:pharmacology; D013268:Stimulation, Chemical
D006728:Hormones; D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone