Decreased follistatin gene expression in gonadotroph adenomas.
What growth factors are involved in the pathogenesis of gonadotroph adenomas is not yet known. Activin is one possible candidate because it stimulates growth and differentiation in many cells, including the gonadotroph cell, and it stimulates FSH secretion, characteristic of gonadotroph adenomas. As activin beta B-subunit is expressed in gonadotroph adenomas, we sought to determine whether activin receptor II and follistatin are also expressed. Total ribonucleic acid (RNA) was extracted from 10 gonadotroph adenomas that did not express pit-1 and was reverse transcribed. The resulting complementary DNAs for human activin receptor II and follistatin were amplified by PCR. All 10 adenomas expressed activin receptor II messenger RNA (mRNA), as did nonadenomatous pituitary tissue. Only 2 of the 10 gonadotroph adenomas expressed detectable follistatin mRNA, although all 4 nonadenomatous pituitaries did. Quantitation of follistatin mRNA by competitive reverse transcription-PCR showed that none of the 10 gonadotroph adenomas expressed as much follistatin mRNA as did the 4 nonadenomatous pituitaries, and 8 of the 10 expressed less than 10% as much. Immunospecific staining showed follistatin in the cytoplasm of the gonadotroph cells of all 5 nonadenomatous pituitaries studied, but only faintly in 1 gonadotroph adenoma and not at all in the other 9. These results suggest that pit-1-negative gonadotroph adenomas express less follistatin mRNA and follistatin peptide than do nonadenomatous gonadotroph cells. A consequence could be less binding, and thereby enhanced effectiveness, of activin, contributing to adenoma growth.
Penabad
J L
JL
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6149, USA.
Bashey
H M
HM
Asa
S L
SL
Haddad
G
G
Davis
K D
KD
Herbst
A B
AB
Gennarelli
T A
TA
Kaiser
U B
UB
Chin
W W
WW
Snyder
P J
PJ
D029404:Activin Receptors; D000236:Adenoma / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D005640:Follicle Stimulating Hormone / Q000032:analysis / Q000378:metabolism; D037201:Follicle Stimulating Hormone, beta Subunit; D038681:Follistatin; D015870:Gene Expression; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics*; D006062:Gonadotropins / Q000378:metabolism*; D006801:Humans; D007986:Luteinizing Hormone / Q000032:analysis; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000737:chemistry / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D017978:Receptors, Growth Factor / Q000235:genetics
D037201:Follicle Stimulating Hormone, beta Subunit; D038681:Follistatin; D006023:Glycoproteins; D006062:Gonadotropins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D029404:Activin Receptors; D012194:RNA-Directed DNA Polymerase