CLINICAL STUDY A luteinizing hormone-, alpha-subunit- and prolactin-secreting pituitary adenoma responsive to somatostatin analogs: in vivo and in vitro studies A Saveanu 1 , I Morange-Ramos 2 , G Gunz 1 , H Dufour 3 , A Enjalbert 1 and P Jaquet 1 1 Interactions Cellulaires Neuroendocriniennes, UMR6544, Centre National de la Recherche Scientifique, Institut Fe´de´ratif Jean Roche, Faculte´ de Me´decine Nord, Boulevard Pierre Dramard, Marseille, France, 2 Service d’Endocrinologie and 3 Service de Neurochirurgie, Centre Hospitalier de Marseille, Hoˆpital de la Timone, 264 Rue Saint-Pierre, Marseille, France (Correspondence should be addressed to P Jaquet, ICNE-UMR6544-CNRS, Institut Fe´de´ratif Jean Roche, Faculte´ de Me´decine Nord, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France; Email: jaquet.p@jean-roche.univ-mrs.fr) Abstract Objective: Evaluation of the efficiency of somatostatin analogues in the treatment of a mixed luteinizing hormone (LH)-, a-subunit-, prolactin (PRL)-secreting pituitary adenoma. Design: A 30-year-old woman, with amenorrhaea-galactorrhaea, presented with a pituitary macroadenoma. The endocrine evaluation showed high plasma levels of PRL, LH, and a-subunit inhibited by 65%, 65% and 33% respectively under octreotide test (200 mg, 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 a-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 a-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 a-subunit release. Discussion: In this plurihormonal-secreting adenoma, the high efficacy of somatostatin analogues to inhibit PRL, LH and a-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. European Journal of Endocrinology 145 35–41 Introduction In addition to its known suppressive effects upon growth hormone (GH) and thyrotrophin (TSH) secre- tion, there is some evidence that somatostatin may regulate gonadotrophin release. Such an inhibitory effect is only partial as a 30% luteinizing hormone (LH) suppression by somatostatin was found in normal men (1). In gonadotroph pituitary tumours, somatostatin receptors were identified on the tumour cell mem- branes (2, 3). Indeed, such findings led to the study of the effect of long-term octreotide therapy in patients with pituitary tumours which released luteinizing (LH) and follicle-stimulating (FSH) hormones and/or free a-subunit. If octreotide was poorly effective upon tumour shrinkage, a significant reduction in serum FSH concentrations could be found in two out of four patients under long-term octreotide administration (4). More recently, it was shown by cell culture studies that somatostatin and its analogue, lanreotide, inhibited the proliferation of dispersed human non-functioning pituitary cells (5), which, in their majority, do synthesize LH, FSH or the a subunit (6–8). Such data, even if limited, indicated a possible inhibitory effect of somatostatin or its analogues in some gonadotroph tumours. We report, in a women presenting with a pituitary macroadenoma co-secreting LH, a-subunit and PRL, the efficacy of the somatostatin agonist lanreotide in the control of hormonal hypersecretion. Subsequently, the patient underwent a selective surgical removal of the tumour. In this tumour, the quantitative analysis ISSN 0804-4643 European Journal of Endocrinology (2001) 145 35–41 q 2001 Society of the European Journal of Endocrinology Online version via http://www.eje.org