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Several earlier studies have shown that some human pituitary GH-secreting somatotrophinomas are able to synthesise and release hypothalamic GHRH and it has been proposed that a positive autocrine feedback loop involving this tumor-derived GHRH may participate in tumorigenesis. We have used in-vitro cell culture and exploited an antagonist to GHRH, (Ac-Tyr1,D-Arg2-GHRH (1–29)-amide (GHRH-A), to further...
The proopiomelanocortin (POMC) gene expressed in corticotrophs of the anterior pituitary encodes several biologically active peptides and is primarily under the positive control of hypophysiotropic factors (e.g. corticotropin releasing hormone). Using AtT20 cells as a model, we show that these factors increase levels of POMC primary RNA transcripts representative of a transcriptional activation of...
The heterotrimeric Gs protein–adenylyl cyclase (AC) cascade plays a pivotal role in controlling hormone secretion by endocrine glands. Consequently, deficiency of the alpha-subunit of Gs leads to endocrine hypofunction and hypoplasia in the affected cells whereas AC hyperactivity results from activating point mutations within the Gs-alpha gene. The latter, termed gsp oncogenes, are found primarily...
Cis-unsaturated free fatty acids (FFA) like oleic acid are strong blockers of both basal and stimulated GH secretion in vivo by acting directly on the somatotroph cell. Several lines of evidence suggest that this inhibitory action is the result of a perturbation of the function of several plasma membrane integral proteins. It has been reported recently that cis-FFA are able to block several steps...
In 18 patients with hypothalamo-pituitary diseases aged over 60 years and in 18 sex, age- and BMI-matched healthy subjects, the results of plasma IGF-I and IGF-BP3 levels and the GH response to GHRH+arginine test (GHRH+ATT) were correlated to the results of body composition, serum osteocalcin (OC) and urinary cross-linked N-telopeptides of type I collagen (Ntx) and the bone mineral density (BMD)....
Combined pituitary hormone deficiency (CPHD), including growth hormone (GH), prolactin (Prl) and thyroid-stimulating hormone (TSH) in children is now considered a heterogeneous syndrome. Recent findings on expression of mouse pituitary-specific homeodomain factors demonstrate dependence of adenopituitary ontogeny on interactive expression of these factors, suggesting their involvement in etiology...
The mechanisms underlying the reduction in the GH-releasing activity of GHRPs in aging are still unclear. Aim of our study was to verify in man whether age-related impairment of the neurohormonal control of GH secretion and/or receptor alterations are involved in the reduced GH response to GHRPs in aging. To this goal, in 16 normal elderly subjects (E, 66–81 yr) and 12 young controls (Y, 24–28 yr)...
Estrogen (E2), acting via its nuclear receptors, has been implicated in tumor development and growth, particularly in the pathogenesis of breast cancer. E2 also modulates anterior pituitary hormone production and is a potent cell mitogen. Until recently, the actions of E2 were thought to be mediated by a single estrogen receptor (ER) isoform (ERα), and currently little is known of the pathophysiological...
A European multicentre, open-label 12-month study with Sandostatin® LAR® administered intramuscularly at 4-week intervals was initiated in 151 acromegalics responsive to octreotide. All patients received 3 injections of the 20 mg dose, following which the dose was adjusted to 10 mg in patients with mean 4-hour GH serum concentrations below 1 µg/L (N: 29) and to 30 mg in patients with concentrations...
Aim: Establish the minimal biochemical and radiological examinations necessary and their cost-effectiveness to accurately diagnose the etiology of Cushing's syndrome (CS). Material and Methods: In 71 patients with CS followed between 1982 and 1997 biochemical studies (basal ACTH, 8mg dexamethasone suppression test -HDST-, metyrapone stimulation test -MST-, or inferior petrosal sinus catheterization...
The aim of this study was to evaluate the efficacy of a 6-month treatment with lanreotide (LAN) (60–90 mg/month) alone and combined with cabergoline (CAB) (1.5-3 mg/week) in 10 acromegalic patients previously demonstrated to be poor responders to octreotide (OCT) (0.6 mg/day) alone and combined with quinagolide (CV) (0.6 mg/day). All patients had previously undergone unsuccessful surgery and none...
A 54-years-old woman diagnosed of myotonic dystrophy (MyD) with past medical history of massive post-partum haemorrhage at age 28 and panhypopituitarism was studied. BMI and body composition were determined and we determined baseline serum IGF-I, IGFBP3, insulin and leptin levels and after the IGF-I generation test performed after the administration of 0.1 U/kg/day s.c each evening for 4 days. As...
Background: Antiestrogens are effective in the treatment of estrogen receptor (ER) positive breast carcinoma. The use of antiestrogen therapy in pituitary adenomas, however, has not been explored. This study attempted to identify a population who may benefit from antiestrogen therapy. Materials & Methods: Prolactinomas from 29 patients (10 men, 19 women) were analyzed for ER and Ki-67 labeling...
Pituitary adenomas are members of the family of neuroendocrine cells and tumors which have secretory granules containing chromogranins/secretogranins and other proteins. Pituitary adenomas express the neuroendocrine specific proconvertases PC1 (also known as PC3) and PC2, which are important for the proteolytic processing of chromogranins/secretogranins molecules. We examined the distribution of PC1...
Prolactin-secreting tumors are the most frequently occurring neoplasms in the human pituitary. Although the clinical syndrome associated with prolactinomas is well recognized the molecular and cellular mechanisms leading to cell transformation and development of these tumors remain elusive. In this paper we summarize recent evidence suggesting that both hypothalamic and intrapituitary defects can...
The paper concisely reviews the data on the humoral factors which regulate the anterior pituitary cell proliferation in endocrine and/or paracrine manner. Their relevance for pituitary tumorigenesis is also discussed. The role of estrogens, growth factors, neuropeptides, dopamine, interleukins and angiotensins is presented.
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