Insulin-like factor 3: a new circulating hormone related to luteinizing hormone-dependent ovarian hyperandrogenism in the polycystic ovary syndrome.
BACKGROUND
Insulin-like factor 3 (INSL3), a member of the relaxin-insulin family, is produced in the Leydig cells and at reduced levels in ovarian theca interna cells of antra follicles as well as in the corpora lutea and ovarian stroma. Among the factors potentially involved in the stimulation of gonadal expression of INSL3, recent data obtained in rats show an important role of LH. Ovaries from most women affected by polycystic ovary syndrome (PCOS) are characterized by hyperplasia of the theca interna and of cortical stroma and by an increased number of small antral follicles, and the majority of women with PCOS, particularly normal-weight subjects, have LH levels that are above the normal range.


OBJECTIVE
The objective of this study was to investigate INSL3 circulating levels in both normal-weight and overweight-obese PCOS women and the association of INSL3 with gonadotropin and androgenic pattern and with ovarian morphology.


METHODS
This was a controlled study.


METHODS
The study took place at an academic hospital.


METHODS
The participants included 44 PCOS patients (22 normal-weight and 22 overweight-obese) and 44 controls comparable for age and body weight.


METHODS
The main outcome measures included INSL3 serum concentrations, measured by RIA, in PCOS patients and controls and their correlation with clinical and biochemical phenotype and with ovarian morphology.


RESULTS
INSL3 serum concentrations were significantly higher in PCOS patients with respect to controls (P = 0.003), particularly in normal-weight (P = 0.001) but not in overweight-obese (P = 0.312) PCOS patients. INSL3 serum concentrations were positively correlated with total and free testosterone and with LH levels in all women (total testosterone, P < 0.001; free testosterone, P = 0.001; LH, P = 0.002) as well as in PCOS patients (total testosterone, P = 0.024; free testosterone, P = 0.045; LH, P = 0.049). Moreover, in the PCOS group, INSL3 levels were related to a greater 17OH-progesterone response to buserelin (P = 0.015), an index of ovarian hyperandrogenism. Finally, in PCOS women, INSL3 levels were positively correlated with ovarian follicle number (P = 0.028).


CONCLUSIONS
INSL3 could be considered a new circulating hormone related to LH-dependent ovarian hyperandrogenism, particularly in normal-weight PCOS women.
Gambineri
Alessandra
A
Division of Endocrinology, Department of Internal Medicine, S Orsola-Malpighi Hospital, Via Massarenti 9, Bologna, Italy.
Patton
Laura
L
De Iasio
Rosaria
R
Palladoro
Federica
F
Pagotto
Uberto
U
Pasquali
Renato
R
D000293:Adolescent; D000328:Adult; D001835:Body Weight; D005260:Female; D006801:Humans; D017588:Hyperandrogenism / Q000209:etiology / Q000378:metabolism*; D007328:Insulin / Q000097:blood*; D007986:Luteinizing Hormone / Q000097:blood*; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D006080:Ovarian Follicle / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000378:metabolism*; D011506:Proteins; D049629:Waist-Hip Ratio
D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; D007986:Luteinizing Hormone