Expression of CRABP1, GRP, and RERG mRNA in clinically non-functioning and functioning pituitary adenomas.

BACKGROUND: Pituitary tumors account for approximately 10-15% of intracranial neoplasms. AIM: Using the cDNA microarray method, we have previously compared expression under two distinct conditions: a pool of 4 clinically non-functioning pituitary adenomas (NFPA) and a spinal cord metastasis of a non-functioning pituitary carcinoma, in order to gain biological insights into genomic changes of pituitary neoplasias. In the present study, we further investigated the mRNA expression of 3 selected genes previously described as being involved in other neoplasias based on a series of 60 pituitary adenomas: CRABP1 (cellular retinoic acid binding protein 1), GRP (gastrin-releasing peptide), and RERG (Ras-related, estrogen- regulated, growth inhibitor). MATERIAL AND METHODS: The expression of CRABP1, GRP, and RERG was determined by quantitative RT-PCR. RESULTS: A significantly higher content of CRABP1 mRNA was observed in NFPA compared to functioning adenomas, and PRL-secreting adenomas showed a lower expression of this gene compared to normal pituitary. A lower expression of GRP mRNA was detected in NFPA compared to normal pituitary and also to functioning adenomas. RERG mRNA was overexpressed in NFPA in comparison to functioning adenomas and to normal pituitary. Among the functioning adenomas, only the ACTH-secreting adenomas presented a higher expression of RERG mRNA compared to normal pituitary. CONCLUSIONS: The findings of differential expression of CRABP1 in prolactinomas and of RERG in NFPA compared to normal pituitary suggests that retinoic acid and estrogen receptor, respectively, could be involved in the tumorigenesis of these adenomas subtypes. Additional studies are required to further confirm this hypothesis.

Plasma cholesteryl ester transfer protein and lipoprotein levels during treatment of growth hormone-deficient adult humans.

The incidence of atherosclerosis is increased in growth hormone (GH) deficient-individuals. Nonetheless, the antiatherogenic benefits of GH replacement therapy remain uncertain. In this study the effect of human recombinant growth hormone (hrGH) replacement therapy administered to GH-deficient adults on the plasma cholesteryl ester transfer protein (CETP) concentration and activity was analyzed. These findings were related to changes in the concentrations of the plasma lipoproteins. The hrGH was administered for 12 mon to human GH-deficient patients (n = 13; 8 men, 5 women). During the study plasma lipoproteins were separated by ultracentrifugation, and plasma cholesterol esterification rate (CER), endogenous CETP activity, and CETP concentration were measured. GH replacement therapy transiently (at 3 mon) lowered plasma concentration of CETP and low density lipoprotein-cholesterol (LDL-C) and raised total triglycerides. Furthermore, hrGH permanently increased both the plasma lipoprotein(a) [Lp(a)] concentration, which is known as atherogenic, and the proportion of cholesteryl ester in the high density lipoprotein2 (HDL2) particles, which is potentially atheroprotective. The simultaneous decrease of the plasma CETP and LDL-C concentrations elicited by hrGH indicated a close relationship between LDL metabolism and the regulation of the CETP gene expression. Endogenous CETP activity and the CER were not modified because these parameters are regulated in opposite ways by plasma levels of triglycerides; that is, CER increased and CETP decreased.

Evaluation of free insulin-like growth factor-I measurement on the diagnosis and follow-up treatment of growth hormone-deficient adult patients.

OBJECTIVE: Insulin-like growth factor (IGF-I) and IGF binding protein-3 (IGFBP-3) are GH-dependent and their concentrations have been used in the diagnosis of GH deficiency. Recently, the free fraction of IGF-I has received more attention. The aim of the study was to assess the role of free IGF-I in the diagnosis of GH deficiency in adults, and in follow-up during treatment with recombinant human GH (rhGH). DESIGN AND PATIENTS: We studied 24 adult patients with pituitary disease and GH deficiency and 25 matched controls. Nine patients were re-evaluated after 6 months of treatment with rhGH (0.25 U/kg/week). MEASUREMENTS: Serum levels of IGF-I, free IGF-I, IGFBP-3 and IGFBP-1 were measured by immunoradiometric assay. RESULTS: Serum free IGF-I levels were significantly lower in the GH deficient group than in the normal group (mean: 0.84 and 1.32 micrograms/l respectively, P = 0.0009). Furthermore, serum IGF-I levels were also lower (mean: 92.24 and 230.47 micrograms/l respectively, P < 0.0001). 63% of patients had serum IGF-I concentration below the normal range. For free IGF-I, 52% of the GH deficient patients showed levels below the lowest value obtained for the normal group. Seventy-five percent of the patients showed at least one of the two determinations below the normal range. The free-total IGF-I ratio was significantly higher (P = 0.025) in GH deficient group (range: 0.19-21.29, mean: 2.53) than in normal controls (range: 0.2-2.15, mean: 0.6). Regarding IGFBP-3 and IGFBP-1 no differences were observed between the two groups. During rhGH treatment the increase in serum total and free IGF-I and IGFBP-3 paralleled the beneficial effects on body composition. CONCLUSIONS: Free IGF-I may be another useful method for the diagnosis of GH deficiency, particularly if related to total IGF-I concentration.

[Sexual disorders in epilepsy. Results of a multidisciplinary evaluation]. / Alterações sexuais na epilepsia. Resultados de uma avaliação multidisciplinar.

Eleven epileptic men who complained of epilepsy and sexual dysfunction were submitted to a multidisciplinary evaluation. Mean age was 27 years (20-34), mean epilepsy duration was 19 years (0.5-32) and the mean seizure frequency was two by week (0-7). Ten patients had partial seizures and one other had myoclonic epilepsy. Ten patients were treated with antiepileptic drugs (phenytoin--1, carbamazepine--8, clonazepam--3, clobazam--2, valproic acid--3, vigabatrin--1). As defined in the DSM III-R, the complaints were: erectile disorder (9), hypoactive sexual desire disorder (4), frotteurism (4), inhibited orgasm (3), premature ejaculation (3), fetishism (2), voyeurism (2), exhibitionism (2), pedophilia (1) and sexual aversion disorder (1). Two patients showed hypogonadotropic hypogonadism on endocrinologic screening. Urological evaluation disclosed organic erectile dysfunction in other two. One patient had a diagnosis of psychogenic sexual disorder. In six patients a conclusive etiologic diagnosis was not reached. This report shows the multifactorial nature of sexual disorder in epilepsy and underlies the need of a multidisciplinar evaluation.

The desmopressin stimulation test in the differential diagnosis of Cushing's syndrome.

OBJECTIVE: We assessed the ability of desmopressin to stimulate the pituitary-adrenal axis in patients with Cushing's syndrome. DESIGN AND SUBJECTS: The cortisol response to 5 ot 10 micrograms of intravenous desmopressin was evaluated in 31 patients with Cushing's syndrome of several aetiologies and in 15 normal subjects. RESULTS: Cortisol responses were observed in 15 out of 16 patients with pituitary dependence and in two patients with adrenal nodular hyperplasia, the increase above baseline ranging from 61 to 379% in the responders. Eight patients with adrenal tumours and one with the ectopic ACTH syndrome did not respond to desmopressin, having shown changes in their cortisol levels from -5 to 42% above baseline. Responses occurred in two out of the 15 normal individuals, whose cortisol increased 58 and 69% above baseline, respectively. Stimulation tests with standard agents as lysine vasopressin or ovine corticotrophin-releasing hormone were performed in the same patients and there was a high degree of concordance. No serious adverse reactions were observed in the tests with desmopressin. CONCLUSIONS: Desmopressin was able to stimulate the pituitary-adrenal axis in patients with Cushing's disease and, like corticotrophin releasing hormone, it may prove useful in the differential diagnosis of Cushing's syndrome.