Somatostatin receptors on thyrotropin-secreting pituitary adenomas: comparison with the inhibitory effects of octreotide upon in vivo and in vitro hormonal secretions.
The in vivo and in vitro inhibitory effects of a somatostatin (SRIH) analog, octreotide, upon TSH, alpha-subunit, GH, and PRL have been studied, as well as SRIH receptors and their coupling to adenylate cyclase, in nine TSH-secreting pituitary adenomas. From in vivo and cell culture studies, the TSH- and alpha-subunit-secreting adenomas appeared heterogeneous, with four out of the nine tumors cosecreting GH and/or PRL. A single sc injection of octreotide (100 micrograms) lowered plasma concentration of TSH by 40 +/- 5% (mean +/- SE of 5), of alpha-subunit by 27 +/- 9% (n = 5), of GH by 60 +/- 5% (n = 4), and of PRL by 27 +/- 9% (n = 4). In cells cultures, octreotide (10(-8) mol/L) inhibited equally TSH, alpha-subunit, and GH release. 125I-Tyr0-DTrp8-SRIH binding sites were measurable in the nine TSH-secreting adenomas either on membrane preparations (n = 6; Bmax: 152 +/- 73 fmol/mg protein) or on frozen sections by radioautography (n = 3). Their density was variable among TSH adenomas and was lower than that measured in GH-secreting adenomas but higher than in nonfunctioning tumors. Two out of three TSH-secreting adenoma displayed an heterogeneous distribution of 125I-Tyr0-DTrp8-SRIH binding sites. 125I-Tyr0-DTrp8-SRIH specific binding was inhibited by guanosine triphosphate (GTP: 10(-4) mol/L). SRIH inhibited adenylate cyclase in 5/5 TSH-secreting adenomas and a good correlation (r = 0.92, P less than 0.02) was found between 125I-Tyr0-DTrp8-SRIH binding capacity (Bmax) and maximal adenylate cyclase inhibition by SRIH. These results demonstrate in vivo and in vitro inhibition of TSH, alpha-subunit, PRL, and GH secretion by octreotide in TSH-secreting pituitary adenomas. Functional SRIH receptors are present on these tumors and the effect of SRIH on hormonal secretion could be mediated, at least in part, by inhibition of adenylate cyclase. These findings support the medical treatment of this rare type of tumors by SRIH analogs.
INSERM U159, Centre P. Broca, Paris, France.
J
J
Bertherat
T
T
Brue
A
A
Enjalbert
G
G
Gunz
R
R
Rasolonjanahary
A
A
Warnet
P
P
Jaquet
J
J
Epelbaum
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D000368:Aged; D001665:Binding Sites; D005260:Female; D006728:Hormones / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000494:pharmacology*; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D017481:Receptors, Somatostatin; D013004:Somatostatin / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D006728:Hormones; D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D013004:Somatostatin; D013972:Thyrotropin; D000262:Adenylyl Cyclases; D015282:Octreotide