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In vitro studies on TSH secretion and adenylate cyclase activity in a human TSH-secreting pituitary adenoma. Effects of somatostatin and dopamine

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Abstract

We have studied the in vitro TSH secretion and the adenylate cyclase (AC) activity of a human pituitary adenoma surgically removed from a hyperthyroid patient showing high serum TSH levels. The tumor appeared almost homogeneously constituted by cells positive for an anti-TSH-beta antiserum and showing the ultrastructural characteristics of the adenomatous thyrotrophs. Adenoma fragments released in vitro a large amount of TSH (148.4 μU/mg prot/30 min), alpha-subunit(35.5 ng/mg prot/30 min) and TSH-beta (10.1 ng/mg prot/30 min). The effects of somatostatin (GHRIH) and dopamine (DA) on the hormone release have been tested in vitro. Both agents markedly inhibited the release of intact TSH and TSH-beta whereas the release of alpha-subunit was less affected. The two agents were effective at concentrations higher than 10−8M. The ability of GHRIH and DA in modulating the AC activity was investigated in membrane fraction preparations. GHRIH inhibited AC at concentrations higher than 10 −7M. The maximal inhibition was 32% at 10−5 M. Conversely, DA slightly stimulated AC activity. This effects was not mimicked by the dopaminergic ergot CH 29–717, which was completely ineffective on the enzyme. These results suggest that: 1) in this TSH-secreting pituitary adenoma a normal secretory response to the inhibiting agents (GHRIH and DA) is present; 2) different mechanisms of transduction of the GHRIH and DA signals (cAMP dependent and cAMP independent) could be operating in this tumor.

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Authors and Affiliations

  1. Facoltà di Medicina, Università di Milano, Milano, Italy

    A. Spada (Cattedra di Endocrinologia e Medicina Costituzionale), P. Beck-Peccoz (Cattedra di Endocrinologia e Medicina Costituzionale), A. Sartorio (Cattedra di Endocrinologia e Medicina Costituzionale), L. Vallar (Cattedra di Endocrinologia e Medicina Costituzionale) & G. Faglia (Cattedra di Endocrinologia e Medicina Costituzionale)

  2. Centro CNR per lo Studio della Farmacologia delle Infrastrutture Cellulari, Dipartimento di Farmacologia, Università di Milano, Milano, Italy

    M. Bassetti & G. Giannattasio

  3. Università di Pisa, Italy

    E. Martino (Cattedra di Endocrinologia e Medicina Costituzionale) & A. Pinchera (Cattedra di Endocrinologia e Medicina Costituzionale)

  4. Clinica Medica II, Università di Pisa, Pisa, Italy

    L. Baschieri

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  1. A. Spada
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  4. G. Giannattasio
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  5. P. Beck-Peccoz
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  6. A. Sartorio
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  7. L. Vallar
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  8. L. Baschieri
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  9. A. Pinchera
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  10. G. Faglia
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Spada, A., Bassetti, M., Martino, E. et al. In vitro studies on TSH secretion and adenylate cyclase activity in a human TSH-secreting pituitary adenoma. Effects of somatostatin and dopamine. J Endocrinol Invest 8, 193–198 (1985). https://doi.org/10.1007/BF03348476

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  • DOI: https://doi.org/10.1007/BF03348476

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