Expression of Inhibin .ALPHA., and .BETA.A Subunit and Activin Type II Receptor mRNAs in Various Human Pituitary Adenomas.

Abstract

Abstract. Inhibin and activin are known to be involved in the pituitary hormone secretion as well as proliferation of the pituitary. We studied the expression of inhibin a, and 13A subunit and activin type II receptor (ACTR 2) mRNAs in human pituitary adenomas to determine the significance of inhibin and activin in pituitary hormone secretion. Tumor tissues were homogenized immediately after resection in guanidinium thiocyanate to extract total RNA. PCR was performed with reversely transcripted cDNA and respective amplification primers. DNA bands obtained for inhibin a, f3A and ACTR 2 by agarose gel-electrophoresis were 367, 285, and 389 bp, respectively. Messenger RNAs for inhibin f3A were demonstrated in all of the pituitary tissues studied, namely in 3 GH, 2 ACTH, 6 PRL and 1 FSH producing adenomas and 17 non-functioning adenomas. Inhibin a mRNAs were detected in 10 of 12 functioning adenomas and 15 of 17 non-functioning adenomas. ACTR 2 mRNAs were found in 11 out of 17 nonfunctioning adenomas, but only found in 3 out of 12 functioning adenomas. These results suggested local production of activin, a homodimer of /3-subunits, and inhibin, a heterodimer of a and f3 subunits, in most of the pituitary adenomas regardless of their hormone secretion. On the other hand, a significantly higher incidence of ACTR 2 in non-functioning adenomas than in functioning adenomas suggested that activin had its main site of action in non-functioning adenomas, which could be potential gonadotropinomas.

Inhibin .ALPHA. and .BETA.A Subunit Messenger Ribonucleic Acids Expression in Human Pituitary Adenomas: Studies by Quantitative Reverse Transcription-Polymerase Chain Reaction.

“…In addition, activin has been reported to affect GH [3,4] and FSH [5] secretion from human pituitary adenomas. Along with these observations, several studies [6][7][8] including ours demonstrated the inhibin a subunit [6,8], 13 subunit [7,8] and activin type 2 receptor (ACTR 2) mRNAs expressions [8] in some human pituitary adenomas. All of these findings extended those found in rats [9][10][11][12] 32P labeled antisense primers made by the 5'end labeling methods.…”

“…The oligonucleotide primers and the amplification protocols for each PCR were the same as described previously [8]. Briefly, cDNA generated by reverse transcription from total RNA was amplified for inhibin a and /3A subunits as follows: samples or standard templates obtained from respective PCR products were incubated with specific sense and antisense primers, deoxynucleosidetriphosphates (Pharmacia Biotech Co., Tokyo), AmpliTaq DNA polymerase (Takarashuzou Co., Ohtsu, Japan), PCR buffer (Takarashuzou Co., Ohtsu, Japan), and Quantitative PCR standard curves for a and 1'A subunit mRNAs are shown in Fig.…”

Inhibin .ALPHA., .BETA.A Subunit and Activin Type II Receptor mRNAs Are Expressed in Human Brain Tumors.

“…Coexpression of inhibin a, /3A and ACTR II mRNAs has been reported in human pituitary adenomas [16], Leydig cell tumor cell lines [17] and teratoma cell lines [18]. All of these reports showed that the tumor tissues may have sites for the action of activin and suggested an autocrine or paracrine role of activin.…”

“…Activin type II receptor (ACTR II) was recently cloned and shown to code for proteins comprising intracellular kinase domains with a predicted serine/threonine specificity [15]. Our previous study demonstrated the coexistence of inhibin a and 13A subunit and ACTR II mRNAs in various human pituitary adenomas, particularly gonadotropinomas [16]. Coexpression of mRNAs for the inhibin and activin subunits and ACTR II has also been reported in Leydig cell tumors [17] and a human teratocarcinoma cell line [18].…”

Effects of LHRH, FSH and Activin A on Follistatin Secretion from Cultured Rat Anterior Pituitary Cells.

“…These proteins were not identified in the control study with non-immune serum or preabsorbed antiserum (data not shown). There is accumulating evidence that activin is produced in the pituitary and acts as a local regulator for FSH secretion [6,8,[17][18][19]. The follistatin gene is also expressed in various extragonadal tissues including the pituitary and almost invariably coexists with the activin subunit gene [6,7,20], suggesting that follistatin plays an important role in modulating activin action within these tissues.…”