Biomedical subjects

F Peillon

Publications and source records attributed to F Peillon.

At least 73 records · Page 4Linked to original sources

PubMed1987

Evidence of thyrotropin-releasing hormone (TRH) and TRH-binding sites in human nonsecreting pituitary adenomas.

Immunoreactive TRH (IR-TRH) and TRH-binding sites were sought in nonsecreting pituitary adenomas. [3H]TRH bound specifically to cellular membranes from 11 of 12 such adenomas studied, with a dissociation constant (Kd) of 50 +/- 5 (+/- SEM) nmol/L and a maximum number of binding sites of 76 +/- 16 fmol/mg membrane protein (range, 32-229 fmol/mg protein). IR-TRH was detected in all 8 of the tumors in which it was sought. The identity of the IR-TRH was verified by high pressure liquid chromatography. The tumor IR-TRH concentration varied from 45-248 fmol/mg cell protein (mean, 109 +/- 28 fmol/mg cell protein), about half that in normal human pituitary (229 +/- 55 fmol/mg protein). There was no correlation between the number of binding sites and the IR-TRH content. The role of TRH in nonsecreting pituitary adenomas is unknown at this time.

Adenoma↗

PubMed1986

Somatostatin and regulation of prolactin secretion.

In addition to its classical growth hormone (GH) inhibiting action, somatostatin (SRIF) inhibits prolactin (PRL) secretion in man and rat under specific endocrine conditions. Furthermore, SRIF counteracts the thyrotropin releasing hormone (TRH) and vasoactive intestinal peptide (VIP) stimulated prolactin release from rat adenohypophysis in vitro. Two criteria are needed to demonstrate a physiological role of SRIF in PRL control: specific receptors must be present on prolactin secreting cells, and antagonization of endogenous SRIF must affect PRL secretion in vitro. In fact [125I]N--Tyr--SRIF binds to membranes not only of human GH-secreting adenomas, but also of prolactinomas. Specific binding characteristics are comparable in both cell types, but the density of sites in PRL-secreting adenomas is only one-quarter that in GH-secreting adenomas. In contrast, non-PRL-secreting chromophobe adenomas are devoid of specific binding. On the other hand, administration of SRIF antisera (SRIF-AS) affects both GH and PRL secretion in starved rats (a model in which pulsatile GH secretion is abolished); a marked increase in PRL plasma levels occurs, but the needed SRIF-AS concentration is higher than that for GH disinhibition. This demonstrates that endogenous SRIF may exert a negative control over PRL secretion, although lactotroph cells appear less sensitive to SRIF than somatotrophs. Since the apparent affinity of SRIF binding sites is similar on both GH and PRL secreting cells, at least in human tumor tissues, a lower density of SRIF receptors on PRL cells could account for this reduced responsiveness. Alternatively, different coupling mechanisms may be involved in the two cell types.

Adenoma↗

PubMed1986

Evidence for a specific estradiol binding site on rat pituitary membranes.

Using adenohypophyses from normal female rats, we demonstrate that estradiol binds pituitary membranes to one homogeneous population of sites with high affinity [dissociation constant (Kd) = 0.041 +/- 0.014 nM; n = 6] and low capacity [maximum binding (Bmax) = 13.6 +/- 5.6 fmol/mg protein]. The binding is thermolabile. Association experiments show that the best experimental conditions are an overnight incubation at 0 C. When the amount of proteins is increased more than 0.3 mg/ml of membrane suspension, binding is rapidly nonlinear. The presence of 0.5 M leupeptin does not improve the binding. Extensive washing of the membranes does not decrease the amount of sites, indicating that the binding is not loosely attached to the membranes. Parenthetically, it should be noted that the membrane fraction was devoid of the cytosolic enzyme marker, lactate dehydrogenase. Binding is specific for estrogenic compounds. When 100% specific binding was determined in the presence of 10(-6) M diethylstilbestrol, 17 beta-estradiol, estrone, and estriol displaced total binding by 110, 80, and 75%, respectively. Neither 4-OH-tamoxifen nor dihydrotestosterone, progesterone, or cortisol displaced the binding. Taken together, these data argue in favor of the presence of specific membrane recognition sites for estradiol in the rat pituitary.

Animals↗

PubMed1985

Correlative studies between the presence of thyrotropin-releasing hormone (TRH) receptors and the in vitro stimulation of growth-hormone (GH) secretion in human GH-secreting adenomas.

Specific receptors for TRH were characterized on cellular membranes of 6 out of 13 somatotrophic adenomas obtained from acromegalic patients. These receptors had the same dissociation constant (Kd: 62 +/- 10 nM) as those found in human PRL-secreting adenomas, but their maximal number of binding sites (Bmax: 76 +/- 24 fmol/mg of protein) was six fold smaller. A good correlation was found between the presence of TRH receptors and the in vitro TRH-induced stimulation of GH secretion. The increase in GH release varied from 25 to 200%. It was thus concluded that these receptors are functional. However, why only some of the human somatotrophic adenomas possess TRH receptors and respond to TRH in vitro needs further investigations.

Adenoma↗

PubMed1985

Interaction between somatostatin and TRH on growth hormone secretion in perifused human growth hormone tumor cells.

The interaction between somatostatin (SRIF) and thyrotropin-releasing hormone (TRH) on growth hormone (GH) release has been studied on dispersed somatotrophic tumor cells obtained from 7 acromegalic patients. TRH increased GH secretion in 4 cases and SRIF decreased GH secretion in 5 cases. When TRH and SRIF were concomitantly perifused, SRIF, when active by itself, prevented and reversed the TRH-induced stimulation of GH release, while TRH never antagonized the inhibitory effect of SRIF. We conclude that, in these adenomatous cells, the physiological inhibitory factor (SRIF) overcomes the nonphysiological stimulatory factor (TRH) in the control of GH secretion.

Acromegaly↗

PubMed1985

Surgical treatment of prolactinomas. Short- and long-term results, prognostic factors.

All 347 patients surgically treated for a prolactinoma from January 1, 1976 to December 31, 1982, in the neurosurgical ward of Foch Hospital, were retrospectively studied. The frequency of postoperative normalisation of plasma prolactin (PRL) depends on prolactinoma size, preoperative PRL level, duration of first clinical symptom, previous oestroprogestative contraception, and adenoma necrosis. Postoperative PRL values were normalized in 75% of small prolactinomas (grade 0, 1 or 2) with preoperative PRL values less than 200 ng/ml, and clinical duration less than 5 years (n = 102). There was no operative death and minor morbidity (2.7%). Among the 96 patients with postoperative PRL normalisation, operated between 1976 and 1979, 70 were followed up for an average time of 4.4 +/- 0.2 years. 17% of patients had hyperprolactinemia recurrence with a delay of 1.5 +/- 0.4 years. Postoperative PRL levels near the upper normal limit, and weak PRL response to TRH tests were found to be unfavourable prognostic factors for hyperprolactinemia recurrence. Pregnancy did not increase the risk of recurrence, but could reflect genuine long-lasting remission. Selective adenomectomy remains an interesting treatment for prolactinoma, particularly if the adenoma is small, recent and with PRL moderately increased. The frequency of postoperative PRL normalisation after surgery is less than with bromocriptine, but surgery is the only treatment able to achieve a definitive cure with a low iatrogenic risk.

Adenoma↗

PubMed1985

In vitro and in vivo antagonistic regulation by estradiol and progesterone of the rat pituitary domperidone binding sites: correlation with ovarian steroid regulation of the dopaminergic inhibition of prolactin secretion in vitro.

The influences of in vivo and in vitro estradiol (E2) and progesterone (P) treatments on the characteristics of [3H]domperidone binding to intact and ovariectomized (OVX) rat pituitary membranes were analyzed and compared to the modulation by these steroids of dopamine (DA) inhibition of PRL secretion in vitro from intact and OVX rat pituitaries. Using intact rat pituitaries, high and low affinity binding sites for domperidone were detected; the dose-dependent DA inhibition curve of PRL secretion was biphasic (range, 10(-13) - 10(-10) M DA, IC50 = 6 X 10(-12) M; range, 10(-10) - 10(-6) M DA, IC50 = 2 X 10(-8) M). Using OVX rat pituitaries, only the high affinity sites for domperidone were detected, and the dose-dependent DA inhibition curve of PRL secretion was monophasic (range, 10(-10) - 10(-6) M DA, IC50 = 10(-8) M). E2 and P did not modify the characteristics of the high affinity sites either after in vivo treatment or when directly added to the in vitro binding assay. However, using in vivo and in vitro tests, a modulation of the low affinity sites by E2 and P was demonstrated. When E2 is in excess and P levels are low or undetectable, these sites are not detectable, and P is able to restore there presence. A parallelism has been established between this antagonistic E2 and P regulation and the modulation of DA inhibition of PRL secretion (range, 10(-13) - 10(-10) M DA). When intact rat pituitaries are perifused in the presence of 10(-8) M E2, the biphasic dose-dependent inhibition curve of the control is changed into the monophasic curve of the OVX rat pituitaries. Conversely, when OVX rat pituitaries are perifused in the presence of 10(-6) M P, the monophasic curve of the control is changed into the biphasic curve of the intact rat pituitaries. Thus, the DA inhibition in the range 10(-13) - 10(-10) M might result from an interaction between DA and the low affinity site for domperidone. In summary, the biological regulation of PRL by DA at the pituitary level may be mediated by two different DA sites, one being submitted to an antagonistic E2 and P regulation directly at the membrane level. The consequence of this regulation is that, whereas E2 decreases the sensitivity of the cell to DA, P is necessary for a normal DA response of the lactotroph.

Animals↗

PubMed1985

Somatostatin receptors in human growth hormone and prolactin-secreting pituitary adenomas.

[125I-Tyr]Somatostatin [( 125I-Tyr]SRIH) binding was found in 11 GH-secreting pituitary adenomas [Kd = 0.46 +/- 0.15 (+/- SE) nM; maximum binding, 165 +/- 35 fmol/mg protein). This binding was specific, since it was displaced by somatostatin-14 (SRIH-14), N-Tyr-SRIH-14, and SRIH-28. In contrast, a number of peptides and drugs not structurally related to SRIH, such as bombesin, dopamine, LHRH, met-enkephalin, naloxone, neurotensin, secretin, substance P, TRH, or vasoactive intestinal peptide, did not affect [125I-Tyr]SRIH binding. [125I-Tyr]SRIH specific binding also was found in PRL-secreting pituitary adenomas. The kinetic characteristics of the specific binding were similar to those of GH-secreting adenomas. However, maximal binding was one quarter that of GH-secreting adenomas (37 +/- 9 fmol/mg protein). In contrast, nonsecreting (chromophobe) tumors were devoid of any specific binding. Finally, in acromegaly, the density of [125I-Tyr]SRIH-binding sites in the adenomas was negatively correlated with plasma GH levels before surgery (r = -0.80). This suggests that somatostatinergic control is involved in GH secretion in acromegalic patients.

Acromegaly↗

PubMed1985

Correlation between the number of thyroliberin binding sites, the tumour size and the plasma prolactin level in human prolactin-secreting adenomas.

Basal plasma prolactin (Prl) level, tumour size and [3H]thyroliberin (TRH) binding to tumour membranes were studied in 18 patients bearing Prl-secreting adenomas. Big tumours (grade III) were associated with high plasma Prl levels (median value: 1929 (range: 207-3570) ng/ml) and possessed numerous membrane TRH receptors (median value: 508 (range: 0-1200) fmol/mg of protein). By contrast, smaller tumours (grade II and I) were associated with lower plasma Prl levels (median values: 1085 (range: 40-1890) and 295 (range: 98-788) ng/ml, respectively) and possessed fewer membrane TRH receptors (median values 122 (range: 11-328) and 13 (range: 0-52) fmol/mg of protein, respectively). A direct positive correlation was demonstrated between the plasma Prl level and the number of [3H]TRH binding sites (rho: 0.729 P less than 0.001). That the higher number of TRH receptors is associated with the largest tumours may be of importance in hyperprolactinaemia and should be taken in account when speculating on the pathogenesis of human Prl-secreting adenomas.

Adenoma↗

PubMed1984

Paradoxical response of thyrotropin to L-dopa and presence of dopaminergic receptors in a thyrotropin-secreting pituitary adenoma.

We studied the dopaminergic control of TSH secretion in a patient with hyperthyroidism due to a TSH-secreting pituitary adenoma. A 34-yr-old previously thyroidectomized woman had mild clinical hyperthyroidism and a diffuse goiter without exophthalmos. She complained of headaches and had bitemporal hemianopsia. Serum T4 and T3 by RIA were elevated, and TSH was 112 microU/ml (normal range, 1.1-7.2). The alpha-subunit to TSH molar ratio was 1.7 (normal, less than 1), as reported in other patients with tumoral TSH hypersecretion. After TRH, a marked increase in TSH occurred. There was no evidence of pituitary deficiency. Skull x-rays and computerized axial tomography revealed an intrasellar tumor with suprasellar extension. Selective transsphenoidal adenomectomy was performed, and a pituitary tumor was removed. The tumor was almost entirely composed of cells reactive with antihuman beta TSH serum by indirect immunofluorescence. A unique feature of this patient was the marked increase in TSH levels after L-dopa administration. To our knowledge, this paradoxical response has never been reported previously in such patients. Using [3H]domperidone as ligand, dopaminergic receptors were demonstrated in the membranes of the adenomatous thyrotroph cells. The reason for the paradoxical response of TSH to dopaminergic agents is not known.

Adenoma↗

PubMed1983

Biochemical and functional alterations of central GABA receptors during chronic estradiol treatment.

The characteristics of GABA and benzodiazepine receptors were examined in the hippocampus, striatum and cerebral cortex of female rats at various times (up to 9 months) after the subcutaneous implantation of an estradiol pellet (10 mg). A significant decrease in the Bmax of the high-affinity binding of [3H]muscimol to membranes from these 3 regions was detected as soon as one week after the implantation. Although the characteristics of the high-affinity binding of [3H]flunitrazepam remained unaffected during the whole treatment, the stimulatory effect of GABA (and muscimol) on this binding was significantly reduced by estrogenization. The changes in GABA receptor binding appeared functionally relevant since the elevation of striatal acetylcholine levels normally induced by the peripheral administration of muscimol (5 mg/kg) was significantly lower in estradiol-treated than in control female rats. In contrast to that observed in intact female rats, the implantation of estradiol in hypophysectomized animals did not affect the characteristics of [3H]muscimol binding to hippocampal, striatal and cortical membranes. [3H]muscimol binding was also unchanged in female rats implanted with estradiol and treated chronically with bromocriptine for 3 weeks. Since both hypophysectomy and the chronic administration of bromocriptine suppressed the hyperprolactinemia normally induced by estrogenization, the down-regulation of central GABA receptors very likely involved prolactin in intact animals implanted with 17-beta-estradiol.

Acetylcholine↗

PubMed1983

Failure of 2 Hydroxyestradiol to interact with dopamine inhibition of human prolactin secretion in vitro and with dopamine receptors of prolactin-secreting adenomas.

The ability of 2-Hydroxyestradiol, a catecholestrogen, and 17 beta Estradiol to interact with the dopamine inhibition of prolactin and with dopamine receptors has been tested on dispersed human prolactin-secreting cells obtained from ten pituitary adenomas. There is a 80% inhibition of prolactin secretion obtained by addition of dopamine in a superfusion system. This inhibition is not affected by preexposure to the steroids, or by their introduction into the perifusion medium. Moreover 2 Hydroxyestradiol and 17 beta Estradiol do not interact with the binding of 3H Domperidone to DA receptors.

Adenoma↗

PubMed1983

[Presence of high-affinity binding sites for thyroliberin in human pituitary adenomas secreting prolactin].

Specific high affinity binding sites for thyrotropin-releasing hormone (TRH) were demonstrated on cellular membranes from human prolactin-secreting adenomas in spite of the lack of in vivo prolactin response to TRH. One binding site was characterized. The mean value for the Kd from four adenomas was 64.8 +/- 12.5 nM. The maximal number of binding sites varied from one adenoma to another (from 80 to 450 fmoles/mg membrane proteins).

Adenoma↗

PubMed1983

Modifications of the high and low affinity pituitary domperidone-binding sites in chronic estrogenized rats.

The effect of chronic estrogen treatment on the anterior pituitary domperidone-binding sites was studied in female rats. The rats were implanted from 1-6 months with a Silastic capsule containing 17 beta-estradiol. The Feldman analysis of [3H]domperidone binding to anterior pituitary membranes of control or estrogenized rats revealed the presence of two sites. The binding characteristics of the higher affinity site were identical for both groups (Kd of the high affinity site, 0.30-0.45 nM; maximum number of binding sites of the high affinity site, 74-95 fmol/mg protein); however, those of the lower affinity site were affected by the estrogen treatment: the Kd of the low affinity site increased from 17.4 +/- 3.2 to 41.5 +/- 9 (+/- SE) nM, and the maximum number of binding sites of the low affinity site increased from 214 +/- 22 to 343 +/- 35 fmol/mg protein. Thus, in chronic estrogenized rats, the total number of binding sites was increased by 54%. These changes, induced by chronic estrogenization, were reversible, since 2 weeks after removal of the 17 beta-estradiol pellet, the binding characteristics were no longer different from those observed in control rats. In contrast to chronic estrogen treatment, ovariectomy reduced markedly the total number of [3H]domperidone-binding sites in anterior pituitary membranes (-70%). Feldman analysis revealed that this reduction resulted from the complete disappearance of the low affinity sites in those membranes. No significant change in the binding characteristics of the high affinity site was detected in ovariectomized rats. Since estradiol induces a decrease in the anterior pituitary content of dopamine, a denervation supersensitivity-like mechanism might be responsible for the increase in pituitary domperidone-binding sites in estrogenized rats. Conversely, a hyposensitivity mechanism could be implicated in the decrease in the total number of the pituitary domperidone-binding sites in ovariectomized rats, since pituitary dopamine levels are increased in those animals. Whether the antidopaminergic properties of estrogen are also involved in this modulation after chronic estradiol treatment requires further investigation.

Animals↗

PubMed1983

Evidence of receptors for thyrotropin-releasing hormone in human prolactin-secreting adenomas.

Specific receptors for TRH were demonstrated on cellular membranes from 8 out of 10 human PRL-secreting adenomas. One binding site was characterized. The mean (+/- SD) value for the dissociation constant (Kd) from 8 adenomas was 68 +/- 7 nM. The maximal number of binding sites varied from 1 adenoma to another (from 50-1200 fmol/mg protein). In 7 of the 8 patients, there was little or no in vivo plasma PRL response to TRH although receptors for TRH were present on their tumors. It is thus suggested that in vivo absence of stimulatory effect of TRH in human PRL-secreting adenomas is not due to the absence of TRH receptors.

Adenoma↗

PubMed1982

Exaggerated prolactin response of thyrotropin-releasing hormone in women with anovulatory cycles: possible role of endogenous estrogens and effect of bromocriptine.

Twenty-one women 18 to 36 years old, presenting with chronic anovulation, were compared with 10 normally cycling women. The patients were characterized by low progesterone (P) levels (0.93 +/- 0.14 ng/ml versus 15.5 +/- 1.4 in controls), whereas 17 beta-estradiol (E2) was moderately decreased (110.2 +/- 8.3 pg/ml versus 162.8 +/- 14.5 in controls) realizing a relative hyperestrogenism. Basal prolactin (PRL) levels were not elevated (12.1 +/- 0.97 ng/ml versus 9.2 +/- 0.7 in controls), but after thyrotropin-releasing hormone (TRH) stimulation an exaggerated response was observed (114.5 +/- 7 ng/ml versus 55.8 +/- 9 in controls). Patients were treated with bromocriptine (1.25 mg 2 times a day) for 3 months. Fifteen responded with ovulatory cycles, and five became pregnant. Progesterone increased significantly (10.2 +/- 1.3 ng/ml), whereas in patients who did not ovulate P increased only slightly (1.56 +/- 0.18 ng/ml). The particular endocrine profile of these patients (P/E2 imbalance) realizing relative hyperestrogenism may be responsible for the exaggerated PRL response to TRH. Bromocriptine, in reducing this transient, or masked, hyperprolactinemia, allows in many patients the return to ovulatory cycles. This mechanism may be one of the possible pathways leading to chronic functional or organic hyperprolactinemia.

Adolescent↗

PubMed1982

Evidence of dopamine receptors in human growth hormone (GH)-secreting adenomas with concomitant study of dopamine inhibition of GH secretion in a perifusion system.

Dopamine (DA) is known to influence human GH release both in vivo and in vitro. The direct control of GH secretion at the pituitary level has been observed using human GH-secreting pituitary adenomas in organ culture, but no dose-response relationship between DA and GH inhibition was demonstrated. Such a dose-response relationship was obtained using GH-secreting adenomatous cells in a perifusion column. The IC50 of DA was 5 X 10(-8) M. Binding studies with [3H]apomorphine on human GH-secreting pituitary adenoma membranes demonstrated the presence of a dopaminergic receptor (Kd = 0.73 +/- 0.24 nM; maximum binding, 18.5 +/- 3.6 fmol/mg protein), which presumably mediates the effect of DA on GH release. In comparison to prior studies with PRL-secreting adenomas, several differences were apparent: 1) the maximum inhibition of GH release by DA is lower than that of PRL (50% vs. 80%), 2) the maximum number of binding sites is much lower (5-20 times) in GH-secreting adenomas than in PRL-secreting adenomas, and 3) [3H]domperidone does not show specific binding on GH-secreting adenomas but does on PRL-secreting adenomas. These experimental results indicate that the dopaminergic control of GH secretion is different from that of PRL secretion, as DA is less effective on GH release than on PRL release from human pituitary adenomas.

Adenoma↗

PubMed1980

Estrogen receptors in human pituitary adenomas.

Estrogen-binding proteins were observed in the cytosol of human pituitary adenomas. The Kd for estradiol was 0.44 nM at 0 C, and hormonal specificity was that expected for estrogen receptors. Sucrose gradient sedimentation experiments revealed that receptors from different tumors existed in either the 8S or the 4S form or both. Of the 23 tumors examined, 14 contained estrogen receptors. Receptors were more often present and their concentration was higher in PRL-secreting adenomas (mean +/- SEM, 20.6 +/- 13.4 fmol/mg proteins; 7 determinations) than in GH-secreting adenomas (1.4 +/- 0.8 fmol/mg protein; 9 determinations) and chromophobe tumors (4.1 +/- 1.6 fmol/mg protein; 7 determinations). There was also a correlation between the presence of estrogen receptors and histological signs of cell proliferation and tumor growth.

Adenoma↗