Hormonal control of thyrotropin and growth hormone secretion in a human thyrotrope pituitary adenoma studied in vitro

Abstract

Abstract. Pituitary thyrotrope tumours are a rare cause of hyperthyroidism. Prior in vitro studies of these tumours have revealed various patterns of differentiation and secretory activity. We have characterized the histological, biochemical, molecular and physiological features of a thyrotrope adenoma in order to define its origin and autonomy. Histochemical and electron micrograph findings confirmed the diagnosis of a thyrotrope cell adenoma. Immunostaining was positive for TSH and GH in the cytoplasm of the adenoma cells. Tissue extracts contained TSH-IR which co-eluted with authentic hTSH when analysed by gel filtration. Tumour fragments studied in a tissue culture system secreted TSH, α-subunit and GH. TRH (30 nmol/l) stimulated TSH and GH secretion. T3 (1.5 nmol/l) inhibited GH release and had no effect on TSH secretion. GnRH (50 nmol/l), dexamethasone (10−4 mol/l), SRIH (1 μmol/l) and TRH-glycine, a tetrapeptide precursor of TRH, stimulated TSH release. Dexamethasone inhibited GH and α-subunit secretion. Stable transcripts for α- and β-subunits of TSH and GH messenger RNAs were detected by molecular hybridization in cytosolic fractions. Immunohistochemistry, in vitro secretory function, and mRNA analysis suggest multidirectional differentiation of the tumour cells. TRH-glycine may have a direct stimulatory effect upon pituitary thyrotropes.

Thyrotropin-Secreting Pituitary Tumors*

“…Such mRNAs were of a size similar to that found in normal pituitary, and the TSH gene transcription site was normal (146,156,221). Moreover, Sanno et al (150) recently screened five TSH-omas with or without associated GH or PRL hypersecretion and found the mRNAs encoding for all three hormones, strengthening the concept that both pure and mixed TSH-omas originate from a multipotential cell.…”

“…Finally, although the measurement of TRH in the circulation has several well known limitations, the tripeptide was found undetectable after pituitary surgery in one patient (156), while high levels were detected in another case (97), a finding that might suggest a possible etiological role of TRH in tumor formation.…”

“…Therefore, mixed TSH/a-subunit adenomas should be included in the classification of central hyperthyroidism. Taking into account only the adenomas not associated with hypersecretion of other pituitary hormones (GH-, PRL-, FSH/ LH-secreting adenomas are, in fact, frequently associated with a-subunit hypersecretion), this tumor type may actually be present in certain TSH-omas, particularly in those presenting with an extremely high (>30) a-subunit/TSH molar ratio (23,35,40,54,79,83,90,120,157,171) or showing clear discrepancies between TSH and a-subunit responses to TRH (reported in 13/62 cases) (33,35,40,41,45,104,107,120,156).…”

Common genetic variation in the 3′-untranslated region of gonadotropin-releasing hormone receptor regulates gene expression in cella and is associated with thyroid function, insulin secretion as well as insulin sensitivity in polycystic ovary syndrome patients

“…In cell cultures of a human thyrotroph adenoma, GnRH can stimulate TSH secretion (Simard et al 1988). There is evidence that GnRH causes the release of TSH from the amphibian pituitary gland, further demonstrating that the GnRH/GNRHR signaling pathway may play an important role in TSH secretion (Okada et al 2009).…”

Thyrotropin-Secreting Adenoma in an Adolescent Girl without Increased Serum Thyrotropin-alpha

“…This sug gests that synthesis and/or secretion of TSH and TSH-a may have been under differential control within a single adenoma cell. Support for this hypothesis is found in a study of cultured cells from a TSH-secreting adenoma [11]. However, in our case, immunohistochemical studies would not have distinguished a cell type secreting TSH-a alone from one secreting intact TSH.…”