NARRATIVE ABSTRACTTo assess the involvement of ovarian-derived regulatory proteins in FSH modulation, we compared FSH, inhibin A, inhibin B, activin A and follistatin in 79 women from the following five groups: young cycling (YC), older cycling (OC), perimenopause (PERI), spontaneous menopause (PM), and surgical menopause receiving estrogen (OVX+ET). Although inhibin B varied as expected by ovarian function, no group differences were observed in activin A, barring a tendency for an increase in PERI, while FS 288 was lower in the PERI, PM and OVX+ET group and negatively correlated with advancing age.The monotropic rise in FSH in the late reproductive years prior to menopause is accompanied by declining inhibin B (1-3) and increasing activin A (2,3) in the presence of unchanged follistatin (FS) (2), suggesting the potential for a net stimulatory effect on FSH regulation. To what extent such changes reflect ovarian aging is unknown, because these peptides are also produced in multiple sites including the pituitary (4-7). To better assess the importance of ovarian aging in FSH modulation by these regulators, we compared circulating levels of inhibin A, inhibin B, activin A, and the neutralizing activin-binding protein, follistatin (FS), in women with functioning ovaries in varying pre and perimenopausal states to those in women of similar age after spontaneous menopause or ovariectomy while receiving estrogen replacement therapy.Prior to initiation of the study, approval of the protocol was obtained from the University of Michigan Hospital's institutional review board for use of human subjects. All participants (n = 79) provided written consent. Sixty-three healthy volunteers ages 40−50 yrs were recruited into the following four study groups: older cycling (OC mean age = 45.9 ± 0.8 yrs, n=17), perimenopause (PERI mean age = 49.0 ± 0.6 yrs, n=21), spontaneous menopause (PM mean age = 49.4 ± 0.6 yrs, n = 10), and surgical menopause receiving estrogen (OVX+ET mean age = 49.0±1.6 yrs, n=15). A fifth group of 16 young cycling women (YC mean age = 23.0±.9 yrs) served as controls. All participants had a body mass index of 20−25, and reported no current medical or psychiatric illness, no current use of sex steroid therapy, no pregnancy or breastfeeding in the past 6 months, no current history of dieting, excessive exercise or smoking. Plasma values for prolactin, testosterone and DHEAS, obtained during the screening visit, were Corresponding author: Nancy King Reame, MSN, PhD 630 168 th Street Columbia University New York, NY 10032 212−305−6761 (phone) 212−305−2139 (FAX) nr2188@columbia.eduAddress reprint requests to: Nancy Reame, MSN, PhD 630 168 th Street Columbia University New York, NY 10032 nr2188@columbia.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its fi...

The directionality of changes in FSH-regulatory proteins supports the notion that FSH-regulatory peptides may contribute to the night-time augmentation of circulating FSH during puberty in girls.

We studied nutrition and GH in eight obese girls, aged 6-11 yr. Blood was sampled every 15 min for 24 h. A 48-h diet providing 25% of assumed caloric needs was imposed, with repeat sampling during the last 24 h. Six nonfasting lean girls were also studied, and their mean GH was 3 times that of the obese girls in the fed state (P = 0.024). Dieting increased mean GH by 60% (P = 0.0028). There was no difference in pulse number for either group, but total secretion for lean girls was 3.9 times greater than that in obese girls during the fed state. With dieting, obese girls increased their total GH secretion by 60% (P = 0.010), but maintained lower total secretion, approximately 40% that of lean girls (P = 0.014). Mean leptin in obese girls in the fed state was 6.2 times greater than mean leptin in lean girls (P = 0.0001), with higher concentrations at night (P < 0.05) and lowering of total mean leptin while dieting. We conclude that in early pubertal obese girls, short-term caloric restriction partially reverses the low GH state that is characteristic of obesity. The change is concomitant with a decrease in leptin and a lessening of circadian differences.

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An inhibin-B-FSH feedback loop exists prior to the onset of puberty in girls older than 5 years. Sex differences in activin-A and inhibin-B concentrations may be responsible for sex differences in serum FSH concentrations.