Growth hormone response to GHRH, GHRP-6 and GHRH + GHRP-6 in patients with polycystic ovary syndrome.
OBJECTIVE
Despite improved diagnostic facilities and advanced in vitro studies, the primary causes of the polycystic ovary syndrome (PCOS) have not been resolved. A defect in the regulation of GH secretion has been suggested in PCOS but the available data are limited and the underlying mechanisms remain unknown. In recent years considerable attention has been devoted to non-classic GH secretagogues and, in particular, to the series of hexapeptides of which GH-releasing peptide (His-D-Trp-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 mechanisms and it has been reported that GHRH + GHRP-6 is a powerful stimulus 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 patients (normal weight and obese) with PCOS in comparison with matched control groups.


METHODS
All subjects were studied three times on different days with GHRH (100 micrograms i.v.), GHRP-6 (90 micrograms i.v.) and GHRH + GHRP-6 (100 micrograms + 90 micrograms).


METHODS
Sixteen women with PCOS and 22 healthy controls were studied. They were divided into four groups according to BMI: Group A (non-obese PCOS, n = 6, age 21.8 +/- 1.7 years, BMI 22.1 +/- 0.8 kg/m2); Group B: (obese PCOS, n = 10, age 21.7 +/- 1.3 years, BMI 32.9 +/- 2.1 kg/m2); Group C (non-obese healthy women, n = 13, age 26.8 +/- 1.5 years, BMI 21.8 +/- 0.6 kg/m2) and Group D (obese healthy women, n = 9, age 29.4 +/- 4.2 years, BMI 35.7 +/- 1.3 kg/m2).


METHODS
Serum GH was measured using a time-resolved fluoroimmunoassay (Delphia, Pharmacia).


RESULTS
After GHRH administration significant 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 were no differences between the same groups in GH peak or AUC after GHRP-6 administration. There were no significant differences in peaks or AUC for GH after GHRH between Groups A and C, nor between Groups B and D. There were significant differences in GH peaks after combined administration 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 (12068 +/- 2323 vs 5997 +/- 1342, P < 0.05). There were no differences in GH peaks or AUC for GH after GHRH + GHRP-6 administration between Groups A and C or Groups B and D.


CONCLUSIONS
The impaired GH response to GHRH found in obese PCOS patients is a consequence of obesity and could be a functional defect, since it can be overridden with GHRP-6 administration.
Micić
D
D
Institute of Endocrinology, Diabetes and Diseases of Metabolism, Beograd, Yugoslavia.
Kendereski
A
A
Popović
V
V
Sumarac
M
M
Zorić
S
S
Macut
D
D
Dieguez
C
C
Casanueva
F
F
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone; D006728:Hormones; D006801:Humans; D009765:Obesity / Q000097:blood / Q000503:physiopathology; D009842:Oligopeptides; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology
D006728:Hormones; D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone