GROWTH-HORMONE RESPONSE TO GHRH, GHRP-6 AND GHRH-6 IN PATIENTS WITH POLYCYSTIC-OVARY-SYNDROME(GHRP)

OBJECTIVE Despite improved diagnostic facilities and advanced in vitro studies, the primary causes of the polycystic ovary syndrome (PCOS) h ave not been resolved. A defect in the regulation of GH secretion has been suggested in PCOS but the available data are limited and the unde rlying mechanisms remain unknown. In recent years considerable attenti on has been devoted to non-classic GH secretagogues and, in particular , to the series of hexapeptides of which GH-releasing peptide (His-D-T rp-Ala-Trp-D-Phe-Lys-NH2, known as GHRP-6) is the most representative. GHRP-6 seems to be a promising tool for exploring GH secretory mechan isms and it has been reported that GHRH + GHRP-6 is a powerful stimulu s to GH secretion, Our aim was to investigate the GH responses to GHRH , GHRP-6 and the administration of GHRP + GHRP-6 in two groups of pati ents (normal weight and obese) with PCOS in comparison with matched co ntrol groups. DESIGN All subjects were studied three times on differen t days with GHRH (100 mu g i.v.), GHRP-6 (90 mu g i.v.) and GHRH + GHR P-6 (100 mu g + 90 mu g). PATIENTS Sixteen women with PCOS and 22 heal thy controls were studied. They were divided into four groups accordin g to BMI: Group A (non-obese PCOS, n = 6, age 21.8 +/- 1.7 years, BMI 22.1 +/- 0.8 kg/m(2)); Group B: (obese PCOS, n = 10, age 21.7 +/- 1.3 years, BMI 32.9 +/- 2.1 kg/m(2)); Group C (non-obese healthy women, n = 13, age 26.8 +/- 1.5 years, BMI 21.8 +/- 0.6 kg/m(2)) and Group D (o bese healthy women, n = 9, age 29.4 +/- 4.2 years, BMI 35.7 +/- 1.3 kg /m(2)). MEASUREMENTS Serum GH was measured using a time-resolved fluor oimmunoassay (Delphia, Pharmacia). RESULTS After GHRH administration s ignificant differences were found between GH peaks in Groups A and B ( 82.4 +/- 16.4 vs 20 +/- 4.9 mU/l, P < 0.05) and in AUC for GH between Groups A and B (4667 +/- 1061 vs 947 +/- 236, P < 0.05) while there we re no differences between the same groups in GH peak or AUC after GHRP -6 administration. There were no significant differences in peaks or A UC for GH after GHRH between Groups A and C, nor between Groups B and D. There were significant differences in GH peaks after combined admin istration of GHRH + GHRP-6 between Groups A and B (211 +/- 26.4 vs 108 +/- 17.6, P < 0.05) as well as between GH AUC in Groups A and B (1206 8 +/- 2323 vs 5997 +/- 1342, P < 0.05). There were no differences in G H peaks or AUC for GH after GHRH + GHRP-6 administration between Group s A and C or Groups B and D. CONCLUSIONS The impaired GH response to G HRH found in obese PCOS patients is a consequence of obesity and could be a functional defect, since it can be overridden with GHRP-6 admini stration.