In vitro secretion of FSH by cultured clinically nonfunctioning and gonadotroph pituitary adenomas is directly correlated with locally produced levels of activin A.
OBJECTIVE
Expression of mRNAs encoding activin and its antagonists inhibin and follistatin has been described in human pituitary adenomas, including clinically nonfunctioning adenomas (NFAs) and gonadotroph adenomas (Gn-omas). Since many of the NFAs and Gn-omas secrete FSH in vitro, we hypothesized that locally produced activin may stimulate secretion of FSH in these pituitary adenomas.


METHODS
Pituitary adenoma tissue was obtained from 38 patients diagnosed preoperatively as having NFAs (n = 17), Gn-omas (n = 5), prolactinomas (n = 6) or growth hormone (GH)-producing adenomas (n = 10). Actual protein levels of activin, inhibin, follistatin, FSH and LH were measured in media of these 38 cultured pituitary adenomas. In addition, we investigated correlations between concentrations of these growth factors and hormones in NFAs and Gn-omas.


RESULTS
Gn-omas were found to secrete significantly more activin A in their culture medium than PRL- and GH-producing adenomas (P < 0.05). Inhibin A and inhibin B protein levels in culture media were very low. A positive correlation between levels of activin A and FSH (r = 0.56, P < 0.005) was found, while no correlation between activin A and LH could be detected. Furthermore, levels of follistatin were positively correlated with activin A levels (r = 0.73, P < 0.0005). Comparison of the activin A:follistatin ratio with the measured FSH protein levels showed an even stronger relationship (r = 0.79, P < 0.0005).


CONCLUSIONS
It is concluded that levels of activin A, follistatin and FSH in media of cultured nonfunctioning adenomas and gonadotroph adenomas are positively correlated. This suggests that these adenomas secrete FSH in response to the relatively high locally produced levels of activin A.
Wessels
H T
HT
Department of Endocrinology & Reproduction, Erasmus University Rotterdam, Rotterdam, The Netherlands. hendrika.wessels@uni-essen.de
Hofland
L J
LJ
van der Wal
R
R
van Gastel
L
L
van Koetsveld
P M
PM
de Herder
W W
WW
de Jong
F H
FH
D028341:Activins / Q000032:analysis / Q000378:metabolism*; D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D003470:Culture Media / Q000737:chemistry; D005260:Female; D005640:Follicle Stimulating Hormone / Q000032:analysis / Q000378:metabolism*; D038681:Follistatin; D006801:Humans; D028322:Inhibin-beta Subunits / Q000032:analysis / Q000378:metabolism*; D007265:Inhibins / Q000032:analysis; D007986:Luteinizing Hormone / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D003470:Culture Media; D038681:Follistatin; C422405:activin A; D028341:Activins; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D028322:Inhibin-beta Subunits