Follistatin and activin A serum concentrations in obese and non-obese patients with polycystic ovary syndrome.
BACKGROUND
Activin promotes ovarian follicular development, inhibits androgen production and increases FSH and insulin secretion. Follistatin, an activin-binding protein, neutralizes activin bioactivity. Therefore, a decrease in the ratio of activin/follistatin might encourage characteristic features of polycystic ovary syndrome (PCOS). We investigated whether women with PCOS showed disordered follistatin and/or activin serum concentrations.


METHODS
The study group included 24 obese and 20 non-obese (body mass index vertical line and <27 kg/m2 respectively) clomiphene-failure PCOS patients. The control group included 16 obese and 46 non-obese patients with normal ovulatory cycles. Blood samples were obtained from the patients on day 3-5 of a progesterone-induced or spontaneous cycle and were assayed for LH, FSH, testosterone, 17-hydroxy-progesterone, androstenedione, follistatin, activin A, fasting glucose and insulin.


RESULTS
Follistatin concentrations were comparable between obese and non-obese PCOS patients (mean +/- SE; 1171 +/- 103 and 1045 +/- 159 pg/ml respectively) and significantly higher than their respective controls (628 +/- 61 and 592 +/- 49 pg/ml, P < 0.0001 and P < 0.02 respectively). Activin A concentrations were comparable between the four groups (590 +/- 35, 513 +/- 74, 661 +/- 87 and 595 +/- 43 pg/ml in obese and non-obese PCOS and controls respectively). Stepwise regression analyses for relationships between follistatin or activin A levels and all other variables indicated that follistatin was significantly and independently positively affected by PCOS (P < 0.0001), age (P < 0.02), androstenedione (P < 0.03) and weight (P < 0.05). Activin A was significantly and independently negatively affected by PCOS (P < 0.003) and FSH (P < 0.03), and positively affected by weight (P < 0.009) and androstenedione (P < 0.02).


CONCLUSIONS
Serum follistatin is increased in PCOS patients, regardless of obesity. PCOS is the most significant variable that relates to high follistatin and low activin A serum concentration. A high follistatin/activin ratio could well contribute to the pathophysiology of PCOS.
Eldar-Geva
T
T
IVF Unit and Institute for Hormone Research, Shaare-Zedek Medical Center, Ben-Gurion University, P.O. Box 3235, Jerusalem, Israel. gevat@szmc.org.il
Spitz
I M
IM
Groome
N P
NP
Margalioth
E J
EJ
Homburg
R
R
D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D028341:Activins / Q000097:blood*; D000328:Adult; D000735:Androstenedione / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D038681:Follistatin; D006801:Humans; D028322:Inhibin-beta Subunits / Q000097:blood*; D007328:Insulin / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D009765:Obesity / Q000097:blood* / Q000150:complications; D010060:Ovulation; D010062:Ovulation Induction; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000150:complications; D011374:Progesterone / Q000008:administration & dosage; D012044:Regression Analysis; D013739:Testosterone / Q000097:blood
D001786:Blood Glucose; D038681:Follistatin; D007328:Insulin; C422405:activin A; D028341:Activins; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D019326:17-alpha-Hydroxyprogesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D028322:Inhibin-beta Subunits