Effects of ghrelin administration on endocrine and metabolic parameters in obese women with polycystic ovary syndrome.
BACKGROUND
The novel peptide ghrelin displays multiple endocrine and non-endocrine actions. Its strong GH-releasing activity in humans has long been recognized. However, in obesity, ghrelin administration induces a blunted GH secretion, enhances glucose and reduces insulin levels. The effects of ghrelin administration have not been investigated in polycystic ovary syndrome (PCOS), which can be associated with obesity, hyperinsulinism, and GH hyposecretion. Leptin is a mediator for energy balance opposed to ghrelin; both of them are supposed to act as regulators of reproductive functions.


OBJECTIVE
Evaluate the endocrine and metabolic response to ghrelin administration in PCOS obese patients compared to body mass index (BMI)-matched and normal weight women.


METHODS
Nine obese PCOS patients (BMI: 35.4+/-1.2 kg/m(2)) (OB PCOS), 6 obese controls (BMI: 38.4+/-1.1 kg/m(2)) (Ob), and 6 normal-weight women (BMI: 23+/-0.6 kg/m(2)) (NW) were enrolled in the study. In all patients we performed: 1) basal hormonal evaluation including FSH, LH, estradiol, testosterone, androstenedione, DHEAS, SHBG, 17-hydroxyprogesterone (17OHP), IGF-I, free T3 (FT3), free T4 (FT4) and ghrelin levels; 2) metabolic evaluation as follows: concentration of non-esterified fatty acid (NEFA) and oral glucose tolerance test (OGTT) (75 g); homeostasis model assessment (HOMA); glucose and insulin response to ghrelin administration (1 microg/kg); 3) measurement of GH, PRL, TSH, and leptin levels after infusion of ghrelin.


RESULTS
Administration of ghrelin increased glucose and reduced insulin levels in both Ob and OB PCOS. Moreover, ghrelin enhanced GH and PRL levels in all groups but it did not modify TSH and leptin levels. GH peak and area under the curve (AUC) in OB PCOS and Ob were lower than controls (p<0.05). Similar PRL peak and AUC values were observed in all groups.


CONCLUSIONS
In both obese and PCOS obese patients, leptin levels are not influenced by ghrelin administration. Moreover, the GH response after ghrelin administration is blunted. However, ghrelin exerts glucose- enhancing and insulin-lowering effects, the latter absent in NW.
Fusco
A
A
Section of Endocrinology, Department of Internal Medicine, Catholic University School of Medicine, 00168 Rome, Italy.
Bianchi
A
A
Mancini
A
A
Milardi
D
D
Giampietro
A
A
Cimino
V
V
Porcelli
T
T
Romualdi
D
D
Guido
M
M
Lanzone
A
A
Pontecorvi
A
A
De Marinis
L
L
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D054439:Ghrelin / Q000494:pharmacology* / Q000502:physiology; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000378:metabolism*; D011388:Prolactin / Q000097:blood; D013972:Thyrotropin / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D011388:Prolactin; D013972:Thyrotropin; D013006:Growth Hormone