A luteinizing hormone-, alpha-subunit- and prolactin-secreting pituitary adenoma responsive to somatostatin analogs: in vivo and in vitro studies.
OBJECTIVE
Evaluation of the efficiency of somatostatin analogues in the treatment of a mixed luteinizing hormone (LH)-, alpha-subunit-, prolactin (PRL)-secreting pituitary adenoma.


METHODS
A 30-year-old woman, with amenorrhaea-galactorrhaea, presented with a pituitary macroadenoma. The endocrine evaluation showed high plasma levels of PRL, LH, and alpha-subunit inhibited by 65%, 65% and 33% respectively under octreotide test (200 microg, s.c.). Long-term treatment with slow release (SR) lanreotide (30 mg/10 days, i.m.) restored menstrual cycles and normalized PRL values. Due to persisting supranormal levels of LH and alpha-subunit, and to the absence of tumoral shrinkage, the adenoma was resected by the transsphenoidal route.


METHODS
In vitro characterization of the somatostatin receptor subtypes (SSTR) expression and functionality. Real-time polymerase chain reaction was performed to quantify the expression of SSTR mRNAs and functionality of the SSTRs was assessed in cell culture studies with various concentrations of native somatostatin (SRIF-14) and of analogues preferential for SSTR2 or SSTR5.


RESULTS
This adenoma presented with high levels of SSTR2, SSTR3 and SSTR5 mRNAs, as compared with a series of gonadotroph adenomas. In cell culture studies, PRL, LH and alpha-subunit were inhibited by 60%, 47% and 33% respectively by SRIF-14 at a concentration of 10 nmol/l. The SSTR2 (BIM-23197, lanreotide) and SSTR5 (BIM-23268) preferential analogues both produced a partial 21-38% inhibition of PRL, LH, and alpha-subunit release.


CONCLUSIONS
In this plurihormonal-secreting adenoma, the high efficacy of somatostatin analogues to inhibit PRL, LH and alpha-subunit secretion in vivo may be explained by the unusually high level of expression and by the functionality of both SSTR2 and SSTR5 receptor subtypes.
Saveanu
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A
Interactions Cellulaires Neuroendocriniennes, UMR6544, Centre National de la Recherche Scientifique, Institut Fédératif Jean Roche, Faculté de Médecine Nord, Boulevard Pierre Dramard, Marseille, France.
Morange-Ramos
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I
Gunz
G
G
Dufour
H
H
Enjalbert
A
A
Jaquet
P
P
D000328:Adult; D000634:Aminoquinolines / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D015292:Glycoprotein Hormones, alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology* / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015175:Prolactinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D017481:Receptors, Somatostatin / Q000145:classification / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use
D000634:Aminoquinolines; D000970:Antineoplastic Agents; C111784:BIM 23197; C121506:BIM 23268; D018491:Dopamine Agonists; D015292:Glycoprotein Hormones, alpha Subunit; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010879:Piperazines; D012334:RNA, Neoplasm; D017481:Receptors, Somatostatin; C060347:lanreotide; D013004:Somatostatin; C046650:quinagolide; D011388:Prolactin