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J B Corcuff

Publications and source records attributed to J B Corcuff.

At least 37 records · Page 2Linked to original sources
PubMed1996

Does functional alteration of the gonadotropic axis occur in endurance trained athletes during and after exercise? A preliminary study.

In men, the hypothalamic-pituitary-testicular axis controls the secretion of testosterone which, in this sex, is a major anabolic hormone. Physical exercise modulates testosterone concentration, affecting the whole axis by poorly understood mechanisms. We have reported in this preliminary study the short and long-term effects of exercise on the function of the gonadotropic axis in trained compared to untrained subjects. Environmental factors known to interfere with pituitary function were minimized. Four marathon and four sedentary men, were studied during 5 days successively using different combinations of two factors: duration and intensity of running tests. Day 0 (D0) was a rest day, and the exercises were: D1 and D2 brief (20 min), light (50% maximal heart rate, HRmax, D1) or intense (80% HRmax, D2), D3 and D4 prolonged (120 min) and light (50% HRmax, D3) or intense (80% HRmax, D4). Testosterone (free and total) and luteinizing hormone (LH) concentrations were measured before, during and after exercise. The baseline concentrations of plasma testosterone were lower in the long distance runners than in the sedentary group [41.8 (SEM 5.5) vs 64.5 (SEM 7.9) pmol.l-1, respectively; P < 0.05]. This phenomenon was centrally mediated as LH concentration was apparently inappropriately low [3.4 (SEM 0.4) vs 4.3 (SEM 1.0) UI.l-1; P > 0.05]. Light to moderate exercise did not modify testosterone and LH concentrations. Conversely, intense and prolonged exercise increased testosterone concentration [73.2 (SEM 9.0) vs 92 (SEM 11.0) pmol.l-1 in the long distance runners and sedentary group, respectively; P < 0.05] and lowered LH concentrations [2.1 (SEM 0.3) vs 3.4 (SEM 0.3) UI.l-1 in the long distance runners and sedentary group, respectively; P < 0.05 compared to D0, at the same time]. In our conditions of exercise, negative feedback of testosterone upon LH persisted, as positive feedback of low testosterone concentrations was apparently lacking (inappropriately low LH concentration with regard to low basal testosterone concentration).

Adult↗
PubMed1995

Pseudo-tumours of the thymus after correction of hypercortisolism in patients with ectopic ACTH syndrome: a report of five cases.

We report the cases of four patients with occult, and one patient with overt, ectopic ACTH syndrome. Cushing's syndrome was cured by removal of the ACTH secreting tumour, op'DDD, ketoconazole or bilateral adrenalectomy. Six to 14 months after remission of hypercortisolism, follow-up computed tomography or magnetic resonance imaging of the thorax revealed in all five patients an anterior mediastinal mass 3-5 cm in length that suggested a thymic carcinoma. Exploratory thoracotomy was performed in four cases and allowed the removal of an enlarged, but normal, thymus. Histological examination revealed no tumour but showed benign thymic hyperplasia with negative immunostaining for ACTH. Thymic enlargement spontaneously disappeared 11 months after its demonstration in the patient who did not undergo thoracotomy. The mechanism of this abnormality is thought to be thymic depletion resulting from high plasma cortisol concentrations followed by 'rebound' thymic hyperplasia when cortisol levels fall. Physicians involved in the management of patients with Cushing's syndrome must be aware of this entity in order to avert a diagnostic thoracotomy.

ACTH Syndrome, Ectopic↗
PubMed1995

Tumor-related selection of calcium signals in vasopressin-stimulated human adenomatous corticotrophs.

The action of arginine vasopressin (AVP) on cytosolic free calcium concentration ([Ca2+]i) was studied at the single-cell level in corticotrophs cultured from pituitary adenoma fragments removed from eight patients with Cushing's disease. AVP evoked distinct [Ca2+]i responses with regard to the tumor origin. In cells from two tumors, AVP consistently evoked a series of characteristic elevations of [Ca2+]i (transient pattern) that depended on Ca2+ entry. In cells from the other tumors, AVP triggered different patterns of [Ca2+]i rise, which consisted of low-amplitude slow monophasic increases at low AVP concentration and a high-amplitude spike increase followed by a sustained plateau (spike-plateau pattern) at higher concentration of AVP. Slow monophasic increases and the spike of spike-plateau responses were due to calcium release from internal stores, whereas the plateau was a consequence of calcium entry. These two patterns (transient vs. spike-plateau) resemble those observed in subpopulations of corticotrophs from healthy rat pituitary glands (Corcuff et al., J. Biol. Chem. 268: 22313-22321, 1993), suggesting that tumorigenesis can lead in pituitary tissues to a selection rather than alteration of AVP [Ca2+]i signals.

Adenoma↗
PubMed1995

[Lp(a) and weight loss in obese patients].

High concentrations of lipoprotein (a) (Lp(a)) are associated with an increased risk of atherosclerotic vascular disease. Lp(a) synthesis is mainly under genetic control but many endocrine disturbances may modulate Lp(a) plasmatic concentrations. There is no agreement upon Lp(a) variations in patients under a hypocaloric diet. This study was undertaken to assess this point in obese females subjected to a 1100 kcal/d diet. Ninety-two obese patients (42.4 +/- 10.4 yr old, BMI 33.9 +/- 5.6 kg/m2) came once a week as out patients during 9 weeks. Lp(a) concentrations distribution was highly skewed. The threshold Lp(a) concentration for a significant cardiovascular risk is estimated at 0.3 g/l. Concentrations above 0.3 g/l were found in 29/92 patients (31%). If the patients were distributed in 2 groups according to their Lp(a) values (< or = ou > 0.3 g/l), the BMI, total cholesterol or triglycerides were not different. There were no significant correlation between Lp(a) and age, total cholesterol or triglycerides. After 9 weeks BMI and total cholesterol values decreased (-1.6 +/- 3.4 kg/m2 and -0.17 +/- 0.68 mmol/l, respectively). Lp(a) concentrations were unchanged (0.3 +/- 0.3 vs 0.3 +/- 0.3 g/l). There were no significant correlation between Lp(a) variations and age, BMI or initial Lp(a) concentrations. No significant decrease of Lp(a) could be detected even in the sub-group of patients with initial concentrations of Lp(a) > 0.3 g/l or even in a sub-group with Lp(a) > 0.7 g/l (n = 7). Under our conditions, weight loss is not associated with a decrease of Lp(a) concentrations suggesting that in a given obese a single determination is enough to assess his Lp(a)-related atherosclerotic risk.

Adult↗
PubMed1994

Prolactin and growth hormone release and calcium influx are stimulated by galanin within a 'window' range of concentrations in pituitary GH3 B6 cells.

Galanin is widely distributed throughout the rat neural and endocrine system with the highest concentration in the anterior pituitary. The effects of galanin were investigated in rat tumor pituitary cells (GH3/B6). A single stimulation with galanin caused prolactin (PRL) and growth hormone (GH) release within a narrow range of concentrations (10(-11)-10(-9) M). However, secretory responses were not consistently observed upon subsequent galanin stimulation. Galanin triggered a rise in cytosolic Ca2+ (burst in [Ca2+]i transients) with a similar responsiveness. By contrast, no change in PRL mRNA was detectable in response to the peptide. These data suggest that galanin which binds to high-affinity receptors in anterior pituitary cells can exert subtle modulations of pituitary cell functions.

Animals↗
PubMed1993

Multiple cytosolic calcium signals and membrane electrical events evoked in single arginine vasopressin-stimulated corticotrophs.

The action of arginine vasopressin (AVP) on cytosolic free Ca2+ concentration ([Ca2+]i) was investigated in single rat pituitary corticotrophs using indo-1 microfluorimetry, in part in combination with the monitoring of membrane electrical events with the perforated patch-clamp technique. In corticotrophs showing the series of short-lived [Ca2+]i rises (transient pattern) in response to corticotropin-releasing factor, 100 nM AVP evoked either the transient pattern or a [Ca2+]i spike followed by a sustained plateau (spike/plateau pattern). Not all corticotrophs responded to changes in AVP concentration in the same manner. Some cells exhibited a concentration-dependent increase in [Ca2+]i transient activity, whereas others showing the spike/plateau at high AVP concentrations responded to low agonist concentrations by two [Ca2+]i responses: a slow rising step or two to three sinusoidal-like oscillations. Combined [Ca2+]i and patch-clamp recordings as well as manipulation of extracellular Ca2+ showed that both transient pattern and the plateau of spike/plateau response depended on Ca2+ entry mainly through voltage-gated, dihydropyridine-sensitive Ca2+ channels. By contrast, step, oscillations, and spike were due to Ca2+ release from internal stores. These Ca(2+)-mobilizing responses caused the activation of Ca(2+)-activated, apamin-sensitive K+ channels, which led to a membrane hyperpolarization. These results reveal cell-specific [Ca2+]i signals and associated electrical events in individual AVP-stimulated corticotrophs.

Animals↗
PubMed1992

Transient but not oscillating component of the calcium mobilizing response to gonadotropin-releasing hormone depends on calcium influx in pituitary gonadotrophs.

Gonadotropin-releasing hormone (GnRH)-stimulated changes in the cytosolic free Ca2+ concentration ([Ca2+]i) were studied in gonadotrophs cultured from 3-week ovariectomized rat pituitaries. One animal was used per cell preparation. [Ca2+]i was monitored in individual gonadotrophs by dual emission microspectrofluorimetry, using Indo-1 as the intracellular fluorescent Ca2+ probe. A short stimulation with GnRH evoked a complex concentration-dependent Ca2+ response in individual gonadotrophs. 0.1-1 nM GnRH triggered a series of sinusoidal-like [Ca2+]i oscillations superimposed upon a modest slow [Ca2+]i rise--the oscillating response mode--while 10-100 nM GnRH caused a biphasic increase in [Ca2+]i consisting of a monophasic transient and oscillations--the transient/oscillating response mode. Despite the consistency of Ca2+ responses, an inter-preparation heterogeneity of [Ca2+]i oscillations frequency was noticed. Moreover, we observed that, within a given cell preparation, the frequency of [Ca2+]i oscillations was independent of GnRH concentration whereas both peak [Ca2+]i and area under the [Ca2+]i versus time curve were concentration-dependent. Thus, in gonadotrophs, the presence of the GnRH signal would lead to [Ca2+]i oscillations, while the amplitude of the [Ca2+]i responses would code for the concentration of agonist. Both transient and oscillating components of GnRH responses depended on releasing activity of Ca(2+)-sequestering pools in as much as GnRH responses were unaffected by brief removal of external Ca2+, but suppressed by chelating intracellular free Ca2+ with BAPTA. However, prolonged exposure to a Ca(2+)-free medium suppressed the transient component while leaving the oscillating component unaffected. We therefore propose that gonadotrophs employ Ca(2+)-sequestering pools, whose maintenance depends on a slow Ca(2+)-entry, to give an amplitude-coded Ca2+ rise in response to a short GnRH stimulation.

Animals↗
PubMed1992

Voltage-dependent calcium current in human decidual cells and its relation to prolactin secretion.

Human decidual cells synthesize and release decidual PRL (dPRL) immunologically and biochemically identical to human pituitary PRL. However, stimulators and inhibitors of PRL secretion such as TRH, bromocriptine or dopamine have no effect on dPRL release. The evidence for the involvement of Ca2+ in dPRL release is based on contradictory or unclear data. Since little is known about Ca2+ movement in human decidual cells we studied the membrane Ca2+ conductance of cultured decidual cells using the patch-clamp technique in the whole-cell configuration. We report the existence of Ca(2+)-dependent action potentials triggered by hyperpolarizing or depolarizing pulses and blocked by cobalt (Co2+; 5 mM). Spontaneous action potentials were observed in the cell-attached mode and found also to be Co(2+)-sensitive. A tetrodotoxin-insensitive and Ca(2+)-dependent rapidly inactivating inward current was investigated in voltage clamp. Its activation threshold was between -60 and -45 mV. Indo-1 measurements of free intracellular Ca2+ concentrations ([Ca2+]i, 169 +/- 14 nM and 141 +/- 8 nM in short-term culture vs. 149 +/- 5 nM in cells cultured for 3-6 days) showed that decidual cells have spontaneous transient fluctuations of [Ca2+]i and that [Ca2+]i was decreased by Ca2+ channel blockers. The existence of Ca2+ movements in decidual cells in culture is thus demonstrated. The occurrence of action potentials in decidual cells derived from fibroblasts, reputed to be inexitable cells, is an interesting biological observation. However, Ca2+ is not involved in the short-term release of PRL by decidual cells, and its effects on long-term secretion still requires further investigation.

Action Potentials↗
PubMed1992

Comparative value of plasma ACTH and beta-endorphin measurement with three different commercial kits for the etiological diagnosis of ACTH-dependent Cushing's syndrome.

Recent reports suggest that, contrary to radioimmunoassays (RIA), immunoradiometric assays (IRMA) artifactually decrease plasma ACTH levels in patients with the ectopic ACTH syndrome. Discrepancies between RIA and IRMA results may provide a means of discriminating this entity from Cushing's disease. We have compared the results of these two techniques, together with those of a beta-endorphin assay, in 17 patients with Cushing's disease, 9 with the ectopic ACTH syndrome and 30 controls. ACTH-RIA and ACTH-IRMA levels in patients with Cushing's disease were similar (17.5 +/- 2.5 vs 15.1 +/- 2.8 pmol/l) and were correlated (rs = 0.59, p less than 0.01). ACTH-RIA levels in patients with the ectopic ACTH syndrome were higher than ACTH-IRMA levels (27.3 +/- 2.9 vs 14.5 +/- 2.5, p less than 0.01) and these did not correlate. The ACTH-RIA and ACTH-RIA/ACTH-IRMA ratio levels in patients with the ectopic ACTH syndrome were higher than those of patients with Cushing's disease (p less than 0.01), but they overlapped with these in 27 and 31% of cases respectively. Plasma beta-endorphin level was higher in patients with the ectopic ACTH syndrome than in patients with Cushing's disease (81.9 +/- 19.4 vs 26.4 +/- 5.6 pmol/l, p less than 0.01) and was correlated with ACTH only in patients with Cushing's disease. The overlap in beta-endorphin and beta-endorphin/ACTH-IRMA molar ratio levels between the two groups were 19 and 27% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Multihormonal response to corticotropin-releasing hormone in inferior petrosal sinus blood of one patient with Cushing's disease: comparison with in vitro secretion of the tumoral corticotropes.

A multihormonal response to CRH during inferior petrosal sinus sampling in patients with Cushing's disease has recently been described. Whether it reflects multihormonal secretion by the corticotropic adenoma, or secretion by non-tumorous adjacent cells via paracrine mechanisms remains debatable. We have compared the effect of CRH on ACTH, GH, PRL and TSH secretion during inferior petrosal sinus sampling with its effect on the in vitro secretion of the corticotropic adenoma after excision in one case of Cushing's disease. Before CRH injection in vivo results show significant central-peripheral gradients for all hormones but only ACTH lateralized to the side of the tumor. After CRH administration, the petrosal concentrations of all hormones increased preferentially on the side of the adenoma resulting in significant intersinus gradients: 8.1 for ACTH, 2.0 for GH, 1.8 for PRL and 1.5 for TSH. In vitro results: the adenoma cells were immunostainable for ACTH only. In culture, they secreted ACTH only. Addition of CRH to the culture induced a mean increase of 160% in ACTH secretion but GH, PRL and TSH remained undetectable. Our results favor the hypothesis that the multihormonal response to CRH seen during inferior petrosal sinus sampling in Cushing's disease reflects a paracrine stimulation of the adjacent non-tumorous pituitary cells by the corticotropic adenoma.

Adenoma↗
PubMed1991

Histiocytosis X of the hypothalamus.

An unusual case of cutaneous and hypothalamic histiocytosis X (HX) is reported. The hypothalamic involvement occurred as a tumor that mimicked a chiasm glioma on computed tomography angioscanning. Magnetic resonance imaging after gadolinium injection localized the tumor within the third ventricle floor. The HX origin of the tumor was confirmed by histological examination of hypothalamic biopsies obtained by transventricular endoscopy. The results of endocrine evaluation were consistent with anterior panhypopituitarism resulting from a multiple releasing-hormone secretory defect, but there was no diabetes insipidus. This unusual endocrine aspect has not been previously described in the field of hypothalamic HX. Lastly, the tumor was insensitive to low dose megavoltage radiation therapy. This unusual case stresses the superiority of magnetic resonance imaging over computed tomography scanning in the assessment of suprasellar tumors and emphasizes the usefulness of transventricular endoscopy in these cases.

Female↗
PubMed1991

Use of ketoconazole in the treatment of Cushing's disease and ectopic ACTH syndrome.

Ketoconazole, an imidazole derivative which inhibits adrenal steroidogenesis, has been used with success for the metabolic control of Cushing's disease. Few data are available about the use of ketoconazole in the management of the ectopic ACTH syndrome. We have used ketoconazole in eight patients: four patients with Cushing's disease, two patients with overt and two with occult ectopic ACTH syndrome. Among patients with Cushing's disease, reversible hypoadrenalism occurred once. All had full clinical and biochemical regression of the disease for more than 6 months with 400-1200 mg ketoconazole per day. Patients with ectopic ACTH syndrome received 1200 mg ketoconazole per day for at least 2 months. Partial biochemical regression was observed in two and a secondary escape to adrenal blockade in two others. These findings further indicate that ketoconazole is a valuable tool for the metabolic control of Cushing's disease. On the contrary, in ectopic ACTH syndrome, this aim can be impossible to reach with ketoconazole although the reasons for its ineffectiveness remain to be determined.

ACTH Syndrome, Ectopic↗
PubMed1991

Spontaneous and corticotropin-releasing factor-induced cytosolic calcium transients in corticotrophs.

Spontaneous and CRF-stimulated changes in the cytosolic free calcium concentration ([Ca2+]i) were studied in two types of corticotrophs: 1) cultured human ACTH-secreting pituitary adenoma cells (hACTH cells), and 2) identified small ovoid corticotrophs cultured from normal rat pituitaries. [Ca2+]i was monitored in individual corticotrophs by dual emission microspectrofluorimetry using indo-1 as the intracellular fluorescent Ca2+ probe. In hACTH cells, [Ca2+]i measurements were carried out in combination with electrophysiological recordings obtained using whole cell patch-clamp techniques. It was shown that a single spontaneous Ca(2+)-dependent action potential led to a marked transient increase in [Ca2+]i in human tumoral corticotrophs. Spontaneous fluctuations in [Ca2+]i were also observed in unpatched corticotrophs whether derived from human pituitary tumors or normal rat tissue. Based on their striking kinetic features and their sensitivity to external Ca2+, we suggest that these spontaneous [Ca2+]i transients were the consequence of action potential firing. Under separate voltage-clamp (patch-clamp) conditions, tumor corticotrophs showed two Ca2+ current components: a low threshold, rapidly inactivating (T-type) current, and a higher threshold, slowly inactivating (L-type) current. The dihydropyridine Ca2+ channel blocker PN 200-110 (100 nM) abolished the L-type current without affecting the T-type current, while the inorganic Ca2+ channel blocker Cd2+ (200 microM) suppressed both Ca2+ currents. The Na+ channel blocker tetrodotoxin (5 microM) did not affect inward currents in tumor corticotrophs. Both L- and T-type voltage-gated Ca2+ channels were involved in controlling [Ca2+]i transients in both tumor and normal corticotrophs, inasmuch as Cd2+ (200 microM) abolished [Ca2+]i) transients, while PN 200-110 (100 nM) greatly diminished, but did not completely abolish, [Ca2+]i transients. The latter did not appear to depend on a voltage-dependent Na+ influx, since they were unaffected by tetrodotoxin (5 microM). Corticotrophs generate [Ca2+]i transients in response to the hypothalamic secretagogue CRF by acting on their membrane excitability. Indeed, we demonstrated in combined fluorescent and electrophysiological experiments that CRF (100 nM) had a coordinate action on human tumoral corticotrophs comprised of a modest depolarization and an increase in the frequency of both action potentials and subsequent [Ca2+]i transients. A coincident increase in the peak amplitude of the [Ca2+]i transient and after hyperpolarization was also observed in some CRF-stimulated cells. CRF (100 nM) evoked qualitatively similar [Ca2+]i patterns in human tumoral and normal rat corticotrophs not subjected to patch-clamping.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1990

Galanin evokes a cytosolic calcium bursting mode and hormone release in GH3/B6 pituitary cells.

The effects of galanin on secretion and cytosolic free Ca2+ concentration ([Ca2+]i) have been studied in GH3/B6 pituitary cells. Prolactin (PRL) and growth hormone (GH) release was measured in column perifusion experiments; [Ca2+]i was monitored in single cells by dual emission microspectrofluorimetry using indo-1 as intracellular Ca2+ probe. Galanin (0.1-1 nM) caused PRL and GH release coincident with a modest rise in [Ca2+]i. The increase in [Ca2+]i comprises the establishment of characteristic long-lasting bursts of [Ca2+]i transients. Galanin acts on Ca2+ entry through voltage-gated Ca2+ channels since there was no response to the peptide when Cd2(+)-a Ca2+ channel blocker-was added to the bath solution. The stimulation of bursting activity by galanin may provide a fine Ca2(+)-signalling mechanism which maximally stimulates hormone release while avoiding refractory periods.

Animals↗
PubMed1990

Electrophysiological response to thyrotropin-releasing hormone of rat lactotrophs in primary culture.

The response of rat pituitary cells to thyrotropin-releasing hormone (TRH) in primary culture was studied in the whole-cell configuration with the patch-clamp technique. Prolactin (PRL)-containing cells were identified in the culture with a peroxidase-antiperoxidase immunocytochemical method. The cells were cultured from the pituitaries of diestrous (D) and lactating (L) female rats. Membrane electrophysiological properties (resting potential and input resistance) of pituitary cells in primary culture varied widely. Under the recording conditions reported here, the mean resting potential of lactotrophs was about -30 mV. There were spontaneous fluctuations in membrane resting potential (10-15 mV) as well as of membrane input resistance, making these parameters difficult to evaluate accurately. Most of the cells exhibited spontaneous firing activity that was shown to be mainly calcium-dependent. There was no difference between L and D cells in resting membrane electrophysiological properties. TRH (10(-7) M) induced a transient hyperpolarization of the membrane similar to that previously described in the GH3 clonal pituitary cell line. Voltage-clamp studies showed that this hyperpolarization resulted from activation of an outward current, the reversal potential of which ranged from -48 to -86.5 mV. Experimental manipulations of the ionic composition of internal and external recording media suggested that both K+ and Cl- were involved. This hyperpolarizing response was observed both in D and L cells, although L cells had larger and faster responses than D cells. This observation may be of physiological significance because lactotrophs have been reported to exist in various subtypes.

Action Potentials↗
PubMed1990

Plasma concentration of atrial natriuretic hormone during endogenous glucocorticoid hypercorticism.

In vitro studies have shown that glucocorticoids may increase atrial natriuretic-hormone (ANH) synthesis and/or release. This action of glucocorticoids has also been suggested in vivo in patients with Cushing's syndrome. However, in this circumstance, plasma AH elevation might be due to humoral disturbances associated with cortisol overproduction. We studied 16 patients with endogenous hypercorticism and 11 of them after successful treatment. Plasma levels of ANH, plasma renin activity (PRA), aldosterone, desoxycorticosterone (DOC), angiotensin II (AII), cortisol, osmolarity, sodium and potassium, urinary free cortisol (UFC), and blood pressure were measured. Before treatment the mean plasma ANH concentration in patients with Cushing's syndrome was significantly higher than in controls (11.3 +/- 2.6 vs. 4.9 +/- 2.3 pmol/l; p less than 0.001). ANH was correlated with cortisol and UFC (r = 0.715, r = 0.700; p less than 0.05). There was no significant correlation between plasma ANH, PRA, aldosterone, DOC, AII, osmolarity, sodium or blood pressure. After recovery, ANH concentration decreased in all patients and was not different from that of normal subjects (4.9 +/- 2.3 vs. 4.3 +/- 2.6 pmol/l). These results suggest that in Cushing's syndrome, ANH secretion is mainly dependent on the severity of hypercortisolism and independent of the other associated disturbances that we studied.

ACTH Syndrome, Ectopic↗