In vitro studies on TSH secretion and adenylate cyclase activity in a human TSH-secreting pituitary adenoma. Effects of somatostatin and dopamine.
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 microU/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(-8)M. 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(-7)M. 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.
Spada
A
A
Bassetti
M
M
Martino
E
E
Giannattasio
G
G
Beck-Peccoz
P
P
Sartorio
A
A
Vallar
L
L
Baschieri
L
L
Pinchera
A
A
Faglia
G
G
D000236:Adenoma / Q000150:complications / Q000378:metabolism* / Q000648:ultrastructure; D000262:Adenylyl Cyclases / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000209:etiology; D066298:In Vitro Techniques; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000150:complications / Q000378:metabolism* / Q000648:ultrastructure; D011863:Radioimmunoassay; D013004:Somatostatin / Q000494:pharmacology*; D013972:Thyrotropin / Q000378:metabolism*
D004873:Ergolines; D013004:Somatostatin; C018794:CH 29717; D013972:Thyrotropin; D000262:Adenylyl Cyclases; D004298:Dopamine