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Regular Article |
a Departments of Pediatrics, Physiology, and Biostatistics and the Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan 48109-0404
b Monash Institute of Reproduction and Development, Monash University, Clayton, Victoria 3168, Australia
The objective of the present study was to determine to what extent activin participates in setting the level of FSH secretion and if this regulation includes mediation via changes in GnRH secretion. We administered follistatin, the high-affinity binding protein for activin, to five ovariectomized sheep; we reasoned that the resultant binding of follistatin to activin should lower activin bioavailability and FSH secretion. Hypophyseal portal and peripheral blood samples were collected simultaneously at 10-min intervals for 18 h to measure GnRH, LH, FSH, and both activin-free and total follistatin. Six hours into collection, each ewe received 150 µg/kg i.v. of recombinant human follistatin-288. A week later, the same ewes were subjected to a second series of blood collections of similar length (time control). The FSH levels in pituitary portal blood were approximately 8-fold higher than those in the peripheral circulation. The FSH secretory patterns changed minimally during the time-control period. In contrast, follistatin had profound suppressive effects on FSH secretion. Maximal FSH suppression after FS-288 administration occurred at 5–6 h in the pituitary portal (65% suppression) and 9–10 h in the peripheral (48% suppression) circulation. Follistatin had no effect on GnRH or LH secretory patterns. Disappearance of total follistatin (i.e., free follistatin plus activin-bound follistatin) from the circulation was slower (P < 0.05) than that of free follistatin alone, suggesting that some of the follistatin was complexed with circulating activin, thus reducing the bioavailability of activin. The slower clearance of total follistatin and the lack of follistatin effects on GnRH secretion suggest that changes in activin bioavailability dictate the level of pituitary FSH secretion and that this is a pituitary-specific effect.
1 Supported by National Institutes of Health grant HD 34731 and National Health and Research Council of Australia Program grant 973218.
2 Correspondence: Vasantha Padmanabhan, Reproductive Sciences Program, 300 N. Ingalls Bldg., Rm. 1109 SW, Ann Arbor MI 48109-0404. FAX: 734 936 8620; vasantha{at}umich.edu
3 Current address: Department of Animal Sciences, University of Illinois, Urbana, IL 61801
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