PubMed Health⌕ Search

Biomedical subjects

B Delemer

Publications and source records attributed to B Delemer.

At least 19 recordsLinked to original sources
PubMed2006

Clinical characterization of familial isolated pituitary adenomas.

CONTEXT: Familial pituitary adenomas occur rarely in the absence of multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). OBJECTIVE: Our objective was to characterize the clinical and genealogical features of non-MEN1/CNC familial isolated pituitary adenomas (FIPA). DESIGN AND SETTING: We conducted a retrospective study of clinical and genealogical characteristics of FIPA cases and performed a comparison with a sporadic population at 22 university hospitals in Belgium, Italy, France, and The Netherlands. RESULTS: Sixty-four FIPA families including 138 affected individuals were identified [55 prolactinomas, 47 somatotropinomas, 28 nonsecreting adenomas (NS), and eight ACTH-secreting tumors]. Cases were MEN1/PRKAR1A-mutation negative. First-degree relationships predominated (75.6%) among affected individuals. A single tumor phenotype occurred in 30 families (homogeneous), and heterogeneous phenotypes occurred in 34 families. FIPA cases were younger at diagnosis than sporadic cases (P = 0.015); tumors were diagnosed earlier in the first vs. the second generation of multigenerational families. Macroadenomas were more frequent in heterogeneous vs. homogeneous FIPA families (P = 0.036). Prolactinomas from heterogeneous families were larger and had more frequent suprasellar extension (P = 0.004) than sporadic cases. Somatotropinomas occurred as isolated familial somatotropinoma cases and within heterogeneous FIPA families; isolated familial somatotropinoma cases represented 18% of FIPA cases and were younger at diagnosis than patients with sporadic somatotropinomas. Familial NS cases were younger at diagnosis (P = 0.03) and had more frequently invasive tumors (P = 0.024) than sporadic cases. CONCLUSIONS: Homogeneous and heterogeneous expression of prolactinomas, somatotropinomas, NS, and Cushing's disease can occur within families in the absence of MEN1/CNC. FIPA and sporadic cases have differing clinical characteristics. FIPA may represent a novel endocrine neoplasia classification that requires further genetic characterization.

Adenoma↗
PubMed2006

[How to interprete hypercalcitoninemia?].

PURPOSE: Today, calcitonin assay is used for the diagnosis of thyroid medullary cancer in the context of nodular thyroid disease. Calcitonin is an excellent marker of thyroid medullary cancer but some hypercalcitoninemia can also be related to other diseases, such as renal failure, endocrine tumors other than thyroid medullary cancer and sometimes to C cell hyperplasia, which is a not well-defined situation. Recent studies contributed to define calcitoninemia thresholds, which guide decision and avoid excessive invasive treatment. CURRENT KNOWLEDGE AND KEY POINTS: After a brief reminder of physiological role of calcitonin and assays, the difficulties encountered in interpreting hypercalcitoninemia and its potential causes other than thyroid medullary cancer are addressed. Recent studies, on large series, now allow a better knowledge of specificity and sensitivity of calcitonin measurement in patients with nodular thyroid disease and a well-argued management. FUTURE PROSPECTS AND PROJECTS: In the future, calcitonin dosage will be ordered even more frequently, as some authors recommend it for the diagnosis of thyroid nodule. It is up to us to know how to use this remarkable marker, by considering all possible situations of benign hypercalcitoninemia and reserving aggressive treatments for patients who really need them.

Adult↗
PubMed2006

[Traumatic brain injury and pituitary insufficiency].

Until recently, hypopituitarism was not considered as a potential consequence of traumatic brain injury (TBI) since only few case reports were described. However, since 2000, preliminary studies have underlined such an association. Hypopituitarism may occur during the acute phase of TBI, months after or even many years later. Among the multiple deficiencies, GH deficiency appears to be the most frequently observed. However multiple bias are described in such studies, especially the small number of patients analyzed and the diagnosis relying on baseline values. Most recently, some studies analyzed 50 to 100 patients confirming that up to 50% of patients may be affected by such an association and underlined the necessity to propose a prospective evaluation since the evolution of hypopituitarism is highly variable during follow-up. It also appears necessary to describe this association to allow when necessary to secondarily propose hormonal substitutive treatment which might be discussed in such a context.

Adult↗
PubMed2006

[Impact of systemic disease on the pituitary gland].

Systemic diseases located in hypothalamo-pituitary region can slowly induce pituitary deficiency, diabetes insipidus and morphological abnormalities. The aim of this study is to review recent clinical data about diagnosis of these rare diseases, with a focus on granulomatous diseases: histiocytosis and sarcoidosis. Recent clinical studies on histiocytosis have improved our knowledge about endocrine expression of the disease in children and in adults as well. Diabetes insipidus is the most frequent condition, described mainly in children. GH deficiency is the most frequent pituitary deficit in children and adult patients. During neurosarcoidosis, diabetes insipidus is the most frequent condition and gonadotropic deficiency is the most frequent deficit but GH has not been systematically studied. MRI allows visualisation of some lesions and is very useful to follow the disease course. Diagnosis of these diseases is made by clinical evaluation of all the sites and by pathological analysis of biopsies of peripheral lesions. While pituitary hormone replacement therapy does not seem to raise specific problems in these diseases, etiological treatments are not yet available and indications for antimitotic or immunomodulatory treatment are sometimes discussed.

Endocrine System Diseases↗
PubMed2006

[KIMS observational study of GH therapy in GH-deficient adults: 12-month follow-up analysis of the French cohort].

KIMS study is an international, observational study initiated in 1994 in which France has been involved since 2003. Its aim is to collect on a widespread basis long-term data from GH-deficient adults treated or not treated with growth hormone in daily practice. Among 330 patients already enrolled by 128 centers in France at the data lock point for this first interim analysis, 122 patients were followed up for at least 12 months and their results are presented herein. After one year of treatment, IGF-1 level adjusted for age and sex was normalized for 77% of patients naive of GH-treatment, 71% of semi-naive patients and 85% of non naive patients. Lean mass increase was 5.1% and fat mass decrease 5.7%. Quality of life assessed through QoL-AGHDA questionnaire was improved with a median score decrease from 10 to 6. These are the first results available from French patients and suggest that growth hormone is an appropriate indication for adults with severe GH deficiency.

Adult↗
PubMed2003

The changing spectrum of TSH-secreting pituitary adenomas: diagnosis and management in 43 patients.

OBJECTIVE: Our aim was to report the recent changes in diagnosis and management of TSH-secreting pituitary adenomas. METHODS: We retrieved 43 consecutive patients with TSH-secreting pituitary tumors (23 male and 20 female) among 4400 pituitary adenomas followed between 1976 and 2001 in six Belgian and French centers. RESULTS: TSH was elevated in 18/43 and alpha subunit in 13/32 patients. In patients with intact thyroid (n=30), mean free tri-iodothyronine was 13.1 pmol/l (range 3.5-23) and mean free thyroxine was 38.4 pmol/l (range 10.2-62.7). Hyperprolactinemia and acromegaly were associated in 9/43 and 8/43 cases. The number of associated hypersecretions was higher in macroadenomas than in microadenomas (Chi square = 11.2, P<0.01). Two women had sporadic multiple endocrine neoplasia type 1-associated syndrome. The proportion of microadenomas versus macroadenomas was 1/11 (period 1974-1986) and 8/32 (period 1987-2001). Bilateral petrosal sinus sampling, (111)In-pentreotide scintigraphy and ((11)C)-l-methionine positron emission tomography scan confirmed diagnosis in four questionable microadenomas. Macroadenomas with extrasellar extension (31 cases) had a tendency to be medially located. Medical treatment with somatostatin analogs was initiated as first-line treatment in 26 patients. TSH levels were reduced by more than 50% in 23/26 cases. A tumoral shrinkage of more than 20% was observed in 5/13 cases. Surgery was performed in 36 patients. After 1 year, 21 of them (58.3%) met the criteria of surgical favorable outcome. Pituitary radiotherapy (n=8) and somatostatin analogs allowed normalization in cases not cured by surgery. CONCLUSION: Ultrasensitive methods for TSH measurement led to an earlier recognition of TSH-secreting pituitary tumors. In this series, we observed that TSH-secreting pituitary tumors are today more frequently found at the stage of microadenomas, medially located, without associated hypersecretions and needing new exploration methods as compared with older series. This changing spectrum in the presentation of TSH-secreting pituitary tumors and the excellent response to somatostatin analogs has been accompanied by an improvement in the prognosis of the disease.

Acromegaly↗
PubMed2003

[Therapeutic strategies in somatotroph adenomas with extrasellar extension: role of the medical approach, a consensus study of the French Acromegaly Registry].

UNLABELLED: From the first 198 patient files included into the French Acromegaly Registry, we analyzed 68 patients harboring a somatotroph adenoma with extrasellar extension, after exclusion of those treated by stereotactic or conventional radiotherapy. In these patients (including 37 women), aged 21-77 yr. (45.7 +/- 13.3), GH concentrations ranged from 2-260 microg/L (38.6 +/- 44.3), and IGF I from 86-967% of age-matched upper limit of normal (303 +/- 164). Maximal diameter of the adenoma at MRI was 11-36.5 mm (20.4 +/- 6.5), with cavernous sinus involvement in 68% of cases. Three subgroups were defined: 20 patients treated by long-acting somatostatin analogs only (group M), for a mean duration of 3 yr. (extremes 1-7 yr.), 48 patients initially treated by transsphenoidal surgery (group C), of whom 21 were secondarily treated by long-acting somatostatin analogs (group CM) for a mean duration of 1.2 yr. (extremes 0.2-2 yr.). All 3 groups were not statistically different in terms of tumor mass and initial levels of GH and IGF-1. Patients from group M were significantly older than those of the other groups (p<0.05). RESULTS: 46% of patients from group C after surgery vs. 45% of patients from group M had a mean GH below 2.5 microg/L. Biochemical remission (GH<2.5 microg/L and normal IGF1 normal) was obtained in 31% of cases in group C, vs. 25% in group M. In this group, a decrease of the largest tumor diameter was observed in 10 patients (71.5%), ranging from 10-25% in 7 (50%) and exceeded 50% in 3 (21.5%). In group CM, the biochemical remission rate (42%) and final GH or IGF1 values were not significantly different from group M. In conclusion, these data suggest that surgery or long-acting somatostatin analogs have a comparable efficacy in terms of remission rates in somatotroph macroadenomas with extrasellar extensions.

Acromegaly↗
PubMed2002

[Unsuccessful surgery of Cushing's disease. Role and efficacy of fractionated stereotactic radiotherapy].

BACKGROUND AND PURPOSE: To optimize and reduce the toxicity of pituitary adenoma irradiation, we evaluated the feasibility and effectiveness of fractionated stereotactic radiotherapy (FSR) in 51 patients with functional adenoma; 12 of them had Cushing's disease. PATIENTS AND METHODS: Eleven females and one male, median age: 49 years, 8 of them relapsed and 4 had persistent hormonal secretion after surgery. The delivered dose was 50 grays (Gy) (5 x 1.8 Gy/week) using 5 convergent micro-beams scanning in arc therapy mode. The median planned target volume (PTV) receiving 90 to 100% of the total dose was 2,1 cm(3). We used relocatable non-invasive stereotactic device Brain Lab, and adapted Linac for stereotactic radiotherapy. RESULTS: Nine out of twelve patients (75%) presented with complete remission after a median time of 29 months, 3/12 patients with partial remission. Actuarial probability to have hormonal persistent secretion was 88% at on year, 44% from 3 to 5 years, 22% at 7 years, and 11% to 0% after 7 years. The 12-corticotroph adenomas were significantly (p=0.007) more radiosensitive than 39 non-corticotroph adenomas. Toxicity was significantly lower for corticotrope adenoma, with no radio-induced pituitary deficiency and no neurological or optic injury. CONCLUSIONS: Combined surgery and FSR appears to be safe and effective for treatment of pituitary adenomas. However, long-term follow-up is required to determine the impact in terms of tumor response and hormone deficiency. The focused treated volume obtained by FSR seems more suitable for these benign tumours than standard radiotherapy. In addition to this conformal approach, the use of standard fractionation reduced the risk of severe damage to the optic chiasma, which is sometimes observed after radiosurgery and is inherent in single fraction radiotherapy.

Adenoma↗
PubMed2000

Comparison of octreotide acetate LAR and lanreotide SR in patients with acromegaly.

BACKGROUND AND OBJECTIVE: The most effective option for the medical treatment of patients with acromegaly is the use of somatostatin analogues. Long-acting depot formulations for intramuscular injection of two somatostatin analogues have recently become available: octreotide acetate LAR (Sandostatin LAR, Novartis Pharma AG) and lanreotide SR (Somatuline, Ipsen Biotech). We wished to compare efficacy of octreotide LAR and lanreotide SR in acromegalic patients. PATIENTS AND METHODS: A group of 125 patients with acromegaly (67 females; mean age, 47 years; 59 patients had previous pituitary irradiation) from 26 medical centres in France, Spain and Germany were studied. Before the study, all patients had been treated with intramuscular injections of lanreotide SR (mean duration, 26 months) at a dose of 30 mg which was injected every 10 days in 64 and every 14 days in 61 patients, respectively. All patients were switched from lanreotide SR to intramuscular injections of 20 mg of octreotide LAR once monthly for three months. In order to obtain efficacy and safety data of lanreotide SR under study conditions, it was decided to randomly assign at day 1, in a 3 : 1 ratio, the time point of the treatment switch; 27 of the patients were randomly assigned to continue the lanreotide SR treatment for the first 3 months of the study (group A); they were on octreotide LAR 20 mg from month 4-6. The other 98 patients were assigned to be switched to treatment with octreotide LAR 20 mg at day 1 (group B). In group B patients, octreotide LAR treatment was continued until month 6, with an adjustment of the dose based on GH levels obtained at month 3. RESULTS: The mean GH concentration decreased from 9.6 +/- 1.3 mU/l at the last evaluation on lanreotide SR to 6.8 +/- 1.0 mU/l after three injections of octreotide LAR (P < 0.001). The percentages of patients with mean GH values < or = 6.5 mU/l (2.5 microg/l) and < or = 2.6 mU/l (1.0 microg/l) at the last evaluation on lanreotide SR were 54% and 14%, and these values increased after 3 months treatment with octreotide LAR to 68% and 35% (P < 0.001), respectively. IGF-I levels were normal in 48% at the last evaluation on lanreotide SR and in 65% after 3 months on octreotide LAR (P < 0.001). Patients with pre-study pituitary irradiation had lower mean GH and IGF-I concentrations. But the effects of the treatment change did not differ between the irradiated and the nonirradiated patients. In general both drugs were well tolerated. CONCLUSION: Octreotide LAR 20 mg administered once monthly was more effective than lanreotide SR 30 mg administered 2 or 3 times monthly in reducing GH and IGF-I in patients with acromegaly.

Acromegaly↗
PubMed1999

Prognostic factors in patients with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1. Groupe d'Etude des Néoplasies Endocriniennes Multiples (GENEM and groupe de Recherche et d'Etude du Syndrome de Zollinger-Ellison (GRESZE).

BACKGROUND & AIMS: Risk factors of metachronous liver metastases and death are not well known in patients with the Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1. These factors were retrospectively determined in 77 patients. METHODS: Data chart review was performed. RESULTS: Median follow-up was 102 months (range, 12-366). Surgery was performed on 48 patients, including 9 of the 10 patients with large pancreatic tumors (>/=3 cm). Liver metastases developed in 4 patients (40%) with large pancreatic tumors, in 3 (4.8%) without, and in 1 of the 4 patients with pancreatic tumors of unknown size; all had previously undergone surgery. The only independent factor associated with development of liver metastases identified by multivariate analysis was large pancreatic tumors (risk ratio, 29.0; 95% confidence interval [CI], 3. 2-260.7). Surgery was not selected. The probability of being free of liver metastases in the 63 patients without large pancreatic tumors was 96% (95% CI, 88-100) at 10 and 15 years. Thirteen (16.9%) patients died. The only independent factors of death selected by multivariate analysis were Zollinger-Ellison syndrome diagnosis before 1980 (risk ratio, 8.2; 95% CI, 1.7-40.6) and age at diagnosis (risk ratio/year, 1.08; 95% CI, 1.03-1.14). CONCLUSIONS: Large pancreatic tumors are predictive of the development of metachronous liver metastases, and surgery does not seem to prevent them.

Adult↗
PubMed1999

Immunohistochemical study of thrombospondin and its receptors alpha root of beta 3 and CD36 in normal thyroid and in thyroid tumours.

AIM: To describe the pattern of distribution of thrombospondin (TSP1) and its receptors, alpha root of beta 3 integrin and CD36, in normal human thyroid tissue and to compare their expression in different benign and malignant thyroid conditions. METHODS: Immunohistochemistry was used to study TSP1 and its receptors in 40 surgical thyroidectomy specimens (normal parenchyma, 7; follicular adenoma, 4; multinodular goitre, 13; papillary carcinoma, 6; follicular carcinoma, 8; anaplastic carcinoma, 2). RESULTS: In the normal thyroid parenchyma, there was weak expression of TSP1 limited to the vessels with no staining of the extracellular matrix. In goitres, the expression of TSP1 was more pronounced in areas of fibrosis, with staining of alpha root of beta 3 on thyrocytes located in the vicinity. In thyroid adenomas, expression of TSP1 was slightly enhanced compared with normal tissue, located in the basement membrane of vessels. In papillary carcinomas, TSP1 was abundant in the desmoplastic stroma with a cytoplasmic distribution of alpha root of beta 3 integrin in thyrocytes. In follicular carcinomas, TSP1 was less abundant in the extracellular matrix, limited to the vessels of the stroma with a weaker expression of alpha root of beta 3 on thyrocytes than in papillary carcinomas. In anaplastic carcinomas, TSP1 was only present in the numerous capillaries of the stroma, with a marked positivity for alpha root of beta 3 in one case. No immunostaining of thyrocytes is observed with CD36. CONCLUSIONS: These results suggest the importance of the interaction between alpha root of beta 3 integrin and TSP1 during remodelling of the matrix in fibrous goitres with areas of early sclerosis comparable with wound healing. In papillary carcinomas, the overexpression of TSP1 restricted to the stroma suggests protective effects against tumour progression.

CD36 Antigens↗
PubMed1998

Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome predisposing to tumors of the parathyroid, endocrine pancreas, anterior pituitary, adrenal glands, and diffuse neuroendocrine tissues. The MEN1 gene has been assigned, by linkage analysis and loss of heterozygosity, to chromosome 11q13 and recently has been identified by positional cloning. In this study, a total of 84 families and/or isolated patients with either MEN1 or MEN1-related inherited endocrine tumors were screened for MEN1 germ-line mutations, by heteroduplex and sequence analysis of the MEN1 gene-coding region and untranslated exon 1. Germ-line MEN1 alterations were identified in 47/54 (87%) MEN1 families, in 9/11 (82%) isolated MEN1 patients, and in only 6/19 (31.5%) atypical MEN1-related inherited cases. We characterized 52 distinct mutations in a total of 62 MEN1 germ-line alterations. Thirty-five of the 52 mutations were frameshifts and nonsense mutations predicted to encode for a truncated MEN1 protein. We identified eight missense mutations and five in-frame deletions over the entire coding sequence. Six mutations were observed more than once in familial MEN1. Haplotype analysis in families with identical mutations indicate that these occurrences reflected mainly independent mutational events. No MEN1 germ-line mutations were found in 7/54 (13%) MEN1 families, in 2/11 (18%) isolated MEN1 cases, in 13/19 (68. 5%) MEN1-related cases, and in a kindred with familial isolated hyperparathyroidism. Two hundred twenty gene carriers (167 affected and 53 unaffected) were identified. No evidence of genotype-phenotype correlation was found. Age-related penetrance was estimated to be >95% at age >30 years. Our results add to the diversity of MEN1 germ-line mutations and provide new tools in genetic screening of MEN1 and clinically related cases.

Amino Acid Substitution↗
PubMed1996

131I-6 beta-iodomethylnorcholesterol scintigraphy: an assessment of its role in the investigation of adrenocortical incidentalomas.

OBJECTIVE: Most incidentally discovered adrenal tumours ('incidentaloma') are benign adrenocortical adenomas. It has been suggested that 131I-6 beta-iodomethylnorcholesterol (IMC) scan could specify the degree of functional autonomy of such adenomas depending on whether they prevent contralateral adrenal tracer uptake. Our purpose was to examine this hypothesis in a correlated scintigraphic and endocrine study. DESIGN: Prospective study evaluating the prevalence of unilateral IMC uptake (tumour uptake with no visualization of the contralateral adrenal gland) and bilateral uptake (uptake in both the tumoral and the contralateral adrenal glands) in patients with unilateral incidentaloma. Comparison of adrenocortical function and of IMC scan after dexamethasone (DXM) in the two scintigraphic groups thus defined. PATIENTS: Thirty-five patients with a unilateral mass highly suggestive of benign adrenocortical adenoma on CT scan. MEASUREMENTS: The IMC scan was performed in basal conditions (baseline scan) and after DXM (suppression scan). Adrenocortical function assessment included basal measurements of 11-deoxycortisol, 17 alpha-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulphate (DHEAS), plasma cortisol and ACTH, urinary free cortisol (UFC), overnight and low-dose DXM suppression test, and CRH test. RESULTS: The baseline scan showed 16 patients (46%) with unilateral uptake (group A) and 19 (54%) with bilateral uptake (group B). Patients in group A exhibited lower ACTH values at 0800h (P = 0.05) and higher cortisol values after an overnight DXM suppression test (P = 0.02), than did patients in group B. In addition, 3 patients in group A failed the overnight and the low-dose DXM suppression tests. Adrenal masses were larger in group A than group B (P = 0.04) and an inverse correlation was found in the whole population between tumour size and ACTH value at 0800h (P = 0.05). On the suppression scan performed in 14 patients (7 in each group), patients in group A continued to exhibit unilateral tumour uptake and bilateral uptake was suppressed in 72% of patients in group B. An adrenal mass was removed in 3 patients of group A with confirmed benign adrenocortical adenomas. In the post-surgical period, the contralateral gland was again visualized in a baseline scan and the hormonal evaluation returned to the normal range. CONCLUSION: Unilateral 131I-6 beta-iodomethylnorcholesterol tumour uptake is a frequent feature in benign adrenocortical adenomas. Hormonal data and scintigraphic profiles obtained after dexamethasone, as well as hormonoscintigraphic changes observed after surgery, provide evidence that unilateral uptake is related to functioning adenomas with various degrees of autononomy and suggest that the 131I-6 beta-iodomethylnorcholesterol scan could be a valuable tool for screening 'subclinical' Cushing's adenomas.

Adenoma↗
PubMed1994

Cyclic AMP regulation of annexins I, II, V synthesis and localization in cultured porcine thyroid cells.

Porcine thyroid cells cultured in the presence of TSH (0.1 mU/ml) or forskolin (10(-5) M) for 4 days display an increased annexin I, II, V biosynthesis when compared with unstimulated cells. Annexin I mostly accumulates in the cytosolic fraction and annexins II and V in the particulate fraction. TSH and forskolin affect in the same manner annexin biosynthesis and localization. In the TSH and forskolin treated cells PGE2 production is very low in comparison with the very high PLA2 activity observed in the dedifferentiated control cells. A strong inhibition of the PGE2 production is observed in control cells incubated with a purified annexin V preparation. These results suggest the existence, in porcine thyroid cells, of a cross-talk between the adenylyl cyclase system and the phospholipase A2 mediated pathways. Annexins' biosynthesis and localization are under the control of the adenylyl cyclase system and participate in this cross-talk.

Animals↗
PubMed1994

12-O-tetradecanoyl-phorbol-13-acetate (TPA) counteracts the cAMP up-regulation of the expression of the stimulatory guanine nucleotide binding protein (Gs alpha) and Gs alpha messenger RNA in cultured pig thyroid cells.

In this study, we examined whether the protein kinase C (PKC) pathway could interfere with the regulation of Gs protein in porcine thyroid cells. The two days culture of cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) (0.1 microM) alone neither affected adenylyl cyclase activity, nor the level of Gs alpha protein in membranes when compared with control cells. The co-addition of TPA with thyrotropin (TSH) (1 mU/ml) or forskolin (fk) (10 microM) in the culture medium, abolished the stimulatory effects of either agonists on the activation of adenylyl cyclase by fk or [AlF4]- and on the increase of Gs alpha protein. By contrast, TPA had effects neither on the Gi-dependent inhibition of adenylyl cyclase nor on Gi alpha proteins levels. The level of Gs alpha mRNA measured by Northern blot analysis was increased (200%) in TSH- or fk-treated cells and this increase was counteracted by TPA. The effects of TPA observed after 6-9 h of contact with cells were mimicked by mezerezin, a non-phorbol protein kinase C activator and blocked by bisindolylmaleimide a specific protein kinase C inhibitor (GF 109203X). These results suggest that the activation of the PKC pathway prevents the cAMP-dependent up-regulation of Gs alpha protein and Gs alpha mRNA expression.

Adenylyl Cyclases↗
PubMed1993

Roles of LH and insulin resistance in lean and obese polycystic ovary syndrome.

OBJECTIVE: The relationship between insulin resistance and hyperandrogenism led us to study insulin resistance in polycystic ovary syndrome (PCOS) in order to determine its prevalence and pathogenesis. DESIGN: Blood samples were taken on the 8th day after menses commenced. PATIENTS: Sixty-one women with PCOS, 30 with normal weight (BMI < 25 kg/m2) (group 1) and 31 with obesity (BMI > 26 kg/m2) (group 2) were studied. They were divided also according to LH level: group A, low or normal LH (n = 23) and group B, high LH (n = 38). Twenty lean control women and 16 obese control women were studied. MEASUREMENTS: Serum LH, testosterone, free testosterone, dehydroepiandrosterone, sex-hormone binding globulin, androstenedione, and fasting insulin were measured. Insulin sensitivity was explored by the insulin tolerance test (ITT). ITT was performed by bolus i.v. insulin of 0.1 IU/kg. Blood glucose was measured before (-5,0) and after injection (3, 5, 7, 10, 15 minutes). Insulin sensitivity was given by the ratio of glycaemic variation to initial blood glucose (delta G/G index). RESULTS: delta G/G was correlated with other insulin resistance parameters, particularly fasting insulin r = 0.40, P < 0.01. The PCOS groups had the following insulin resistances (mean +/- SEM) compared to matched groups: delta G/G lean PCOS vs lead controls: 0.45 +/- 0.02 vs 0.61 +/- 0.01, P < 0.001; delta G/G obese PCOS vs obese controls: 0.32 +/- 0.02 vs 0.40 +/- 0.01, P < 0.02. Insulin resistance was higher in group A than in group B: delta G/G 0.29 +/- 0.02 vs 0.45 +/- 0.02, P < 0.001. The prevalence of insulin resistance was 63% in lean PCOS and 51% in obese PCOS. Positive correlations between delta G/G index and LH were found in group 1 and 2, respectively r = 0.45, P < 0.01 and r = 0.55, P < 0.01. CONCLUSION: PCOS was associated with a significant decrease of insulin sensitivity, independent of obesity. The correlation between LH and insulin sensitivity suggests a complementary action in PCOS.

Adolescent↗