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.

Abstract. Inhibins and activins have been known to modify the secretion of various pituitary hormones. To study whether inhibins and activins are present in human pituitary tissues, immunohistochemical studies with antisera to activin A and inhibin a subunit were performed on 9 human pituitary adenoma tissue specimens and one sample of normal pituitary tissue adjacent to one adenoma. Activin immunoreactivities were demonstrated in the cytoplasms of one GH and one PRL and two nonfunctioning adenomas and one normal pituitary tissue, but they were negative in one PRL, one ACTH, one FSH and two non-functioning adenomas. Thus, the presence and absence of activin in the same type of adenoma in regard to hormone production, suggested that the difference in immunostaining simply reflected the difference in the activin concentration.In contrast to this, inhibin a subunit immunoreactivity was not found in any of the tissues studied. These data suggested a local synthesis of activin in the normal pituitary as well as various kinds of pituitary adenoma tissues and its local role in the human pituitary gland.

Abstract. Inhibin and activin were initially isolated as regulators of pituitary or gonadal hormone and are now known to be growth factors belonging to the TGF-/3 family with diverse influences on the differentiation and proliferation of various tissues. To investigate the role of inhibin and activin in human brain tumors, the expression of inhibin a, and /3A mRNA as well as activin type II receptor (ACTR II) mRNA were studied in various human brain tumors. The tumors were divided into the following 4 groups: 3 Rathke's cleft cysts and 2 craniopharyngiomas (group 1), 8 meningiomas (group 2), 8 malignant gliomas (group 3), and various other tumors including 1 each of germinoma, astrocytoma, hemangioblastoma, and osteochondroma as well as 2 malignant lymphomas and 2 metastatic squamous cell carcinomas (group 4). Immediately after resection, tumor tissues were homogenized in guanidine thyiocyanate to extract total RNA. PCR was then performed with reverse-transcribed cDNA and the respective amplification primers. DNA bands were obtained by agarose gel electrophoresis. Messenger RNA for the inhibin LA subunit was demonstrated in all of the tissues studied. In contrast, inhibin a subunit mRNA was expressed in 60%, 50%, 75%, and 75% of the tumors in groups 1, 2, 3 and 4, respectively, whereas ACTR II mRNA was demonstrated in 20%, 37.5%, 62.5% and 50% of the tumors in each group. Coexpression of mRNAs for the inhibin a, and 13A subunits and ACTR II occurred in some brain tumors. The levels of inhibin a and ACTR II mRNA tended to be higher in the tumors with a higher grade of malignancy. These results indicate that some human brain tumors express receptors for activin, and that inhibin and activin may play an autocrine or paracrine role in brain tumor tissue.

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Abstract.Inhibin a and NA subunit messenger ribonucleic acid (mRNA) levels were measured quantitatively by reverse transcription-polymerase chain reaction (RT-PCR) in human pituitary adenomas. The inhibin a subunit mRNA levels were undetectably low in cultured adenoma tissues, but F3A mRNA were 0.383 ± 0.074 in 3 GH adenomas, 0.672 ± 0.140 in 3 prolactinomas and 0.957 ± 0.414 molecules/cell in 3 non-functioning adenomas. The addition of 10.8 M activin A decreased the NA mRNA levels within 4 h in 1 of 3 GH adenomas, 2 of 3 prolactinomas and 2 of 3 non-functioning adenomas, though the decreases were not statistically significant. The results showed an abundance of IA subunit mRNA compared with a subunit mRNA in all human pituitary adenomas and a local role for activin in its own production through inhibin 13A mRNA subunit expression.