In vitro effects of ketoconazole on corticotrope cell morphology and ACTH secretion of two pituitary adenomas removed from patients with Nelson's syndrome

1989 ◽  
Vol 121 (2) ◽  
pp. 185-190 ◽  
Author(s):  
L.Jimenez Reina ◽  
A. Leal-Cerro ◽  
J. Garcia ◽  
P.P. Garcia-Luna ◽  
R. Astorga ◽  
...  
Keyword(s):  
Volume Density ◽  
Pituitary Cells ◽  
Acth Secretion ◽  
Nelson’S Syndrome ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Nelson's Syndrome ◽  
In Vitro Effects ◽  
Intracellular Changes

Abstract. The direct effects of ketoconazole on the secretion of ACTH by human pituitary adenoma cells from 2 patients with Nelson's syndrome were studied in vitro. Stereologically quantified, intracellular changes affect the surface density of the endoplasmic reticulum (it decreased by 73%), the volume density of the secretion granules (it decreased by 49%), and the volume density of lysosomes (it decreased by 67%). The hormone released in the culture medium decreased depending on the doses of ketoconazole used; 10 μmol/l decreased ACTH levels by 31%. These data show that ketoconazole induce marked changes on corticotrope morphology and ACTH secretion in pituitary cells obtained from patients with Nelson's syndrome.

scholarly journals Prolactin (PRL)-Releasing Peptide Stimulates PRL Secretion from Human Fetal Pituitary Cultures and Growth Hormone Release from Cultured Pituitary Adenomas1

2001 ◽  
Vol 86 (6) ◽  
pp. 2826-2830 ◽  
Author(s):  
Tami Rubinek ◽  
Moshe Hadani ◽  
Gad Barkai ◽  
Shlomo Melmed ◽  
Ilan Shimon
Keyword(s):  
Primary Cultures ◽  
Pituitary Hormones ◽  
Pituitary Cells ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Human Pituitary ◽  
Cell Adenoma ◽  
In Vitro Effects

The hypothalamic peptide PRL-releasing peptide (PrRP) has recently been cloned and identified as a ligand of an orphan pituitary receptor that stimulates in vitro PRL secretion. PrRP also induces PRL release in rats in vivo, especially in normal cycling females. However, no information on the effects of PrRP in the human is available. To elucidate the role of PrRP in regulating human anterior pituitary hormones, we used human PrRP-31 in primary cultures of human pituitary tissues, including fetal (20–27 weeks gestation) and normal adult pituitaries, as well as PRL- and GH-secreting adenomas. PrRP increased PRL secretion from human fetal pituitary cultures in a dose-dependent manner by up to 35% (maximal effect achieved with 10 nm), whereas TRH was slightly more potent for PRL release. Coincubation with estradiol resulted in enhanced fetal PRL response to PrRP, and GH release was only increased in the presence of estradiol. Although PRL secretion from PRL-cell adenomas was not affected by PrRP, PrRP induced PRL release from cultures of a GH-cell adenoma that cosecreted PRL. PrRP enhanced GH release in several GH-secreting adenomas studied by 25–27%, including GH stimulation in a mixed PRL-GH-cell tumor. These results show for the first time direct in vitro effects of PrRP-31 on human pituitary cells. PrRP is less potent than TRH in releasing PRL from human fetal lactotrophs and is unable to release PRL from PRL-cell adenomas in culture, but stimulated GH from several somatotroph adenomas. Thus, PrRP may participate in regulating GH, in addition to PRL, in the human pituitary.

Effects of two novel dopaminergic drugs, CV 205-502 and CQP 201-403, on prolactin and growth hormone secretion by human pituitary tumours in vitro

1987 ◽  
Vol 116 (2) ◽  
pp. 287-292 ◽  
Author(s):  
Maria S. Venetikou ◽  
Jacky M. Burrin ◽  
Christine A. Woods ◽  
Tom H. Yeo ◽  
Judith Brownell ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Pituitary Cells ◽  
Pituitary Tumours ◽  
Human Pituitary ◽  
Dopaminergic Drugs ◽  
Gh Secretion ◽  
Normal Rat ◽  
In Vitro Effects

Abstract. Two novel dopaminergic drugs, designated CV 205-502 and CQP 201-403 have recently been developed by Sandoz Pharmaceuticals Ltd (Basle, Switzerland). The effects of these drugs on PRL and GH secretion by normal rat and tumorous human pituitary cells in vitro have been investigated. Low doses of both CV 205-502 and CQP 201-403 immediately and profoundly suppressed PRL secretion, which failed to recover up to 7 h after removal of the drugs. Similarly, CQP 201-403 significantly suppressed basal GH secretion by human pituitary somatotropic tumours in culture, and both drugs significantly reduced the stimulatory effect of GHRH. These effects are more potent and longer acting than the previously described in vitro effects of bromocriptine. It is concluded that CV 205502 and CQP 201-403 hold potential for the treatment of patients with hyperprolactinaemia and, possibly, also in patients with acromegaly.

scholarly journals pNET co-secreting GHRH and calcitonin: ex vivo hormonal studies in human pituitary cells

2016 ◽  
Vol 2016 ◽  
Author(s):  
Taiba Zornitzki ◽  
Hadara Rubinfeld ◽  
Lyudmila Lysyy ◽  
Tal Schiller ◽  
Véronique Raverot ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Somatostatin Receptor ◽  
Tumor Resection ◽  
List Type ◽  
Pituitary Cells ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Initial Work ◽  
Pituitary Lesion

Summary Acromegaly due to ectopic GHRH secretion from a neuroendocrine tumor (NET) is rare and comprises <1% of all acromegaly cases. Herein we present a 57-year-old woman with clinical and biochemical features of acromegaly and a 6 cm pancreatic NET (pNET), secreting GHRH and calcitonin. Following surgical resection of the pancreatic tumor, IGF1, GH and calcitonin normalized, and the clinical features of acromegaly improved. In vitro studies confirmed that the tumor secreted large amounts of both GHRH and calcitonin, and incubation of pNET culture-derived conditioned media stimulated GH release from a cultured human pituitary adenoma. This is a unique case of pNET secreting both GHRH and calcitonin. The ability of the pNET-derived medium to stimulate in vitro GH release from a human pituitary-cell culture, combined with the clinical and hormonal remission following tumor resection, confirmed the ectopic source of acromegaly in this patient. Learning points Signs, symptoms and initial work-up of acromegaly due to ectopic GHRH secretion are similar to pituitary-dependent acromegaly. However, if no identifiable pituitary lesion is found, somatostatin receptor scan and further imaging (CT, MRI) should be performed. Detection of GHRH in the blood and in the tumor-derived medium supports the diagnosis of ectopic GHRH secretion. Functional bioactivity of pNET-secreted GHRH can be proved in vitro by releasing GH from human pituitary cells.

scholarly journals miR-26a Plays an Important Role in Cell Cycle Regulation in ACTH-Secreting Pituitary Adenomas by Modulating Protein Kinase Cδ

Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1690-1700 ◽  
Author(s):  
Erica Gentilin ◽  
Federico Tagliati ◽  
Carlo Filieri ◽  
Daniela Molè ◽  
Mariella Minoia ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pituitary Adenoma ◽  
Protein Kinase ◽  
Pituitary Adenomas ◽  
Viable Cell Number ◽  
Pituitary Cells ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Acth Secreting ◽  
Protein Kinase Cδ

Abstract The functional aftermath of microRNA (miRNA) dysregulation in ACTH-secreting pituitary adenomas has not been demonstrated. miRNAs represent diagnostic and prognostic biomarkers as well as putative therapeutic targets; their investigation may shed light on the mechanisms that underpin pituitary adenoma development and progression. Drugs interacting with such pathways may help in achieving disease control also in the settings of ACTH-secreting pituitary adenomas. We investigated the expression of 10 miRNAs among those that were found as most dysregulated in human pituitary adenoma tissues in the settings of a murine ACTH-secreting pituitary adenoma cell line, AtT20/D16v-F2. The selected miRNAs to be submitted to further investigation in AtT20/D16v-F2 cells represent an expression panel including 5 up-regulated and 5 down-regulated miRNAs. Among these, we selected the most dysregulated mouse miRNA and searched for miRNA targets and their biological function. We found that AtT20/D16v-F2 cells have a specific miRNA expression profile and that miR-26a is the most dysregulated miRNA. The latter is overexpressed in human pituitary adenomas and can control viable cell number in the in vitro model without involving caspase 3/7-mediated apoptosis. We demonstrated that protein kinase Cδ (PRKCD) is a direct target of miR-26a and that miR26a inhibition delays the cell cycle in G1 phase. This effect involves down-regulation of cyclin E and cyclin A expression via PRKCD modulation. miR-26a and related pathways, such as PRKCD, play an important role in cell cycle control of ACTH pituitary cells, opening new therapeutic possibilities for the treatment of persistent/recurrent Cushing's disease.

266. Supressor of cytokine signalling 3 regulates IL-11 induced human endometrial stromal cell decidualization

2005 ◽  
Vol 17 (9) ◽  
pp. 109
Author(s):  
E. Dimitriadis ◽  
C. Stoikos ◽  
L. A. Salamonsen
Keyword(s):  
Stromal Cells ◽  
Embryo Implantation ◽  
Cellular Protein ◽  
Pcr Analysis ◽  
Cytokine Signaling ◽  
Pituitary Cells ◽  
Human Pituitary ◽  
Endometrial Stromal Cells ◽  
Socs3 Protein

Decidualization of endometrial stromal cells is critical for embryo implantation and establishment of pregnancy. Locally produced cytokines such as interleukin (IL)-11 enhance decidualization of human endometrial stromal cells (HESC). IL-11 signaling is negatively regulated by suppressor of cytokine signaling (SOCS) proteins. IL-11 stimulates SOCS3 in human pituitary cells. The aim of this study was to examine the role of SOCS3 on IL-11 induced HESC decidualization. Decidualization of HESC was assessed using an in vitro model in which estrogen (E)+progesterone (P) or cAMP was administered for 8 days to cells. Medium was collected for prolactin (PRL) assay (a decidual marker). Cellular protein was extracted for Western analysis and cellular RNA for real-time RT-PCR analysis. SOCS3 was overexpressed in HESC cells and the effect on decidualization assessed. HESC treated with E+P or cAMP secreted PRL from day 6. Treatment of HESC with E+P or cAMP increased the abundance of SOCS3 protein, coinciding with an increase in PRL secretion. cAMP maximally stimulated SOCS3 protein and mRNA during decidualization. Antiprogestin (onapristone) added to E+P or cAMP treated cells at day 6 reduced PRL secretion but had no influence on SOCS3 abundance suggesting that SOCS3 protein was not regulated via the P-receptor pathway. Addition of IL-11 to HESC increased SOCS3 abundance from 1 h. SOCS3 abundance returned to control levels following treatment of cells with IL-11 and IL-11 neutralising antibody. SOCS3 overexpression in HESC treated with cAMP reduced PRL secretion compared to mock- or non-transfected HESC. Furthermore, IL-11 mediated decidualization was diminished by SOCS3 overexpression. We have demonstrated for the first time that SOCS3 regulates IL-11 induced decidualization and that SOCS3 overexpression in HESC disrupts decidualization. This knowledge is important in understanding the mechanisms by which IL-11 promotes decidualization of HESC and thus the formation of decidua, an essential component of a functional placenta.

Effect of cyproheptadine, desmethylcyproheptadine, γ-amino-butyric acid and sodium valproate on adrenocorticotrophin secretion by cultured pituitary tumour cells from three patients with Nelson's syndrome

1983 ◽  
Vol 96 (3) ◽  
pp. 401-406 ◽  
Author(s):  
S. W. J. Lamberts ◽  
T. Verleun ◽  
E. G. Bons ◽  
P. Uitterlinden ◽  
R. Oosterom
Keyword(s):  
Direct Effect ◽  
Sodium Valproate ◽  
Butyric Acid ◽  
Pituitary Tumour ◽  
Tumour Cells ◽  
Acth Secretion ◽  
Nelson’S Syndrome ◽  
Nelson's Syndrome ◽  
Amino Butyric Acid ◽  
Acth Release

The effects of cyproheptadine, desmethylcyproheptadine, serotonin, γ-amino-butyric acid (GABA) and sodium valproate were studied on ACTH secretion by cultured non-enzymatically dispersed pituitary tumour cells from three patients with Nelson's syndrome. Cyproheptadine (1–10 μmol/l) and desmethylcyproheptadine (1–10 μmol/l) suppressed ACTH secretion significantly (P <0·01), while serotonin (10 μmol/l) did not have a direct effect. Serotonin was also not able to reverse the (desmethyl)cyproheptadine-mediated inhibition of ACTH release. Sodium valproate and GABA did not exert a direct effect on hormone release by these cultured pituitary tumour cells. It is suggested that cyproheptadine-mediated inhibition of ACTH release in Nelson's syndrome might be effected by a direct non-serotonin-related effect on the pituitary tumour, while sodium valproate suppresses ACTH release by a suprahypophysial action.

Differential activation of the pituitary-adrenocortical axis after stress in the rat: use of two genetically selected lines (Roman low- and high-avoidance rats) as a model

1989 ◽  
Vol 123 (3) ◽  
pp. 477-485 ◽  
Author(s):  
C.-D. Walker ◽  
R. W. Rivest ◽  
M. J. Meaney ◽  
M. L. Aubert
Keyword(s):  
Glucocorticoid Receptor ◽  
Conditioned Avoidance ◽  
Plasma Corticosterone ◽  
Type I ◽  
Pituitary Cells ◽  
Acth Secretion ◽  
Rapid Acquisition ◽  
Basal Plasma

ABSTRACT We have examined the activation of the pituitary-adrenal axis in two lines of rats, the Roman high (RHA)- and low (RLA)-avoidance rats known to be emotionally different. These rats are selected for rapid acquisition of a conditioned avoidance response (RHA) compared with failure to acquire this response (RLA). In this study the endocrine response (ACTH, corticosterone, aldosterone) of RLA and RHA rats to two types of stress was examined: exposure to openfield stress for 10 min (Op) or exposure to ether vapours for 3 min (E). Basal plasma ACTH concentrations were lower in RLA than in RHA rats (RLA: 110·8 ± 24·5 ng/l; RHA: 252·7 ± 60·8 ng/l, P<0·05) but the absolute values of ACTH reached after both types of stress were comparable between RLA and RHA rats. Plasma corticosterone and aldosterone under resting conditions were not different between RLA and RHA rats. Plasma corticosterone was higher in RLA following openfield stress (P<0·05) while no differences between RLA and RHA were observed after ether stress (RHA: basal = 66±14·nmol/l, Op =384± 55, E= 606± 75; RLA: basal=121±52, Op = 612 ±92, E= 698 ± 89). Stressinduced increases in plasma aldosterone were higher in the RLA line after both types of stress (RHA: basal = 175±36 pmol/l, Op = 546±53, E= 563± 47; RLA: basal = 272 ± 64, Op =1246 ± 91, E= 863 ± 72). Pituitary responsiveness to exogenous corticotrophinreleasing factor (CRF) in vivo and in vitro differed in the two lines: administration of ovine CRF (10 μg/kg body weight, i.p.) resulted in significant increases in ACTH secretion but the response was significantly lower in RHA rats (RHA: 511·1 ±41·5 ng/l; RLA: 831·4 ± 70·3 ng/l, P<0·01). Dispersed pituitary cells from the RHA line exhibited a smaller response to CRF (10 nmol/l) treatment in vitro compared with cells derived from the RLA rats (RHA: 750 ± 83% of control; RLA: 1374 ±79, P<0·01) suggesting differences in pituitary sensitivity to CRF between the two lines. Additional differences at the pituitary level were observed since the type II glucocorticoid receptor population in RHA rats was higher than in RLA rats (RHA: 246±13 fmol [3H]RU28362 bound/mg protein; RLA: 173±18, P<0·01). Similarly, hippocampal type I glucocorticoid receptor population was increased in RHA rats (RHA: 172·2 ± 8·3 fmol [3H]aldosterone bound/mg protein; RLA: 116·7±7·3, P< 0·01). It is concluded that first, differences in pituitary activity between RLA and RHA rats are distinct from changes observed at the adrenal level, secondly, increased stress-induced ACTH output in the RLA line is associated with enhanced pituitary sensitivity to CRF and possibly with diminished corticosterone inhibitory feedback action on CRF and ACTH secretion, and thirdly, the possible involvement of differences in the pattern of CRF secretion between RLA and RHA rats on resting pituitary ACTH secretion cannot be excluded. Journal of Endocrinology (1989) 123, 477–485

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