Ain't misbehavin': reflections on the functional differences among anterior pituitary cells

Schwartz, Jeffrey; Gracia‐Navarro, Francisco

doi:10.1016/0303-7207(96)03898-1

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…Tumour volume was estimated by assuming the volume of a sphere: 4/3 pr 3 . Median (extreme) values were (173 (13-270) mm 3 for microadenomas and 3022 (500-10 312) mm 3 for macroadenomas (P < 0:0001).…”

Section: Patientsmentioning

confidence: 91%

“…Basal thyroid function was normal, except for a lowlevel tri-iodothyronine syndrome observed in patients with a macroadenoma (Table 3). The peak TSHresponse to TRH was significantly lower in patients with a macroadenoma, and inversely correlated with the size (log mm 3 ) of the adenoma (r S ¼ ¹0:64, log mm 3 against mlU/l; P < 0:05). The plasma concentration of insulin-like growth factor-I was also significantly lower in the patients with macroadenoma (Table 3), and negatively correlated with adenoma size (r S ¼ ¹0:75, log mm 3 against IU/l; P < 0:05).…”

Section: European Journal Of Endocrinology (1998) 138mentioning

confidence: 94%

“…Efforts have been made to distinguish functionally or clinically relevant subgroups of Cushing's disease. The disease is of clonal origin in the majority of cases, and subtypes could result from the heterogeneity of normal corticotroph cells (2,3). Classifications have been proposed on the basis of histological (4), radiological (5), biochemical (6) or functional criteria (7,8), but none has so far been widely accepted.…”

Section: Introductionmentioning

confidence: 99%

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Cushing's disease: a comparison of pituitary corticotroph microadenomas and macroadenomas

Selvais

Donckier

Buysschaert

et al. 1998

European Journal of Endocrinology

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Cushing's disease appears as a functionally heterogeneous disease, but criteria that are able to distinguish between different clinical forms remain elusive. We compared two subgroups of patients with proven Cushing's disease according to the size of the pituitary adenoma, evaluated by computed tomography or magnetic resonance imaging. Our series comprised 11 patients with a microadenoma and 10 with a macroadenoma (median volumes (range): 173 (13-270) and 3022 (500-10312) mm 3 respectively; P < 0:0001). The clinical presentation was similar in the two groups, but the time elapsed before diagnosis was longer, and visual impairment was less frequent in the patients with a microadenoma (1:5 Ϯ 0:8 years and 0%) than in those with a macroadenoma (0:7 Ϯ 0:6 years and 40%; P < 0:05). Morning and evening peripheral concentrations of ACTH were greater in patients with macroadenoma (134 Ϯ 78 and 130 Ϯ 7 ng/l respectively) than in those with microadenoma (52 Ϯ 28 and 56 Ϯ 19 ng/l, P < 0:05). Hypokalaemia and lymphopenia were also more pronounced in patients with macroadenoma (3:4 Ϯ 0:3 mmol/l and 1273 Ϯ 401 lymphocytes/mm 3 ) than in those with microadenoma (3:8 Ϯ 0:3 mmol/l and 1852Ϯ668 lymphocytes/mm 3 ; P < 0:05), although morning and evening plasma cortisol concentrations were similar in both groups. In patients with macroadenoma, there was less relative nycthemeral variation of ACTH concentrations (28 Ϯ 24%, compared with 62 Ϯ 39% in those with microadenoma; P < 0:05), less suppression of plasma cortisol by high doses of dexamethasone (¹30 Ϯ 14%, compared with ¹61 Ϯ 25%; P < 0:05), and a reduced concentration ratio of mean basal cortisol to ACTH (7 Ϯ 3, compared with 12 Ϯ 5; P < 0:05). Plasma IGF-I concentration and the TSH peak response to TRH were significantly lower in patients with macroadenoma than in those with microadenoma (0:4 Ϯ 0:2 × 10 3 IU/l and 2:3 Ϯ 1:8 mIU/l, compared with 1:8 Ϯ 0:6 × 10 3 IU/l and 5:2 Ϯ 1:6 mUI/l; P < 0:05). Thus, in comparison with microadenomas, corticotroph macroadenomas are characterized by a greater and more autonomous ACTH secretion, inducing more pronounced biological signs of hypercorticism, and are more often accompanied by visual field defects and impairment of other pituitary hormonal secretions. European Journal of Endocrinology 138 153-159

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Section: Patientsmentioning

confidence: 91%

Section: European Journal Of Endocrinology (1998) 138mentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Cushing's disease: a comparison of pituitary corticotroph microadenomas and macroadenomas

Selvais

Donckier

Buysschaert

et al. 1998

European Journal of Endocrinology

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“…In particular, the tripeptide induces a more pronounced activation of α-MSH secretion, [Ca 2+ ] i increase and POMC mRNA accumulation in LD than in HD melanotrope cells [6]. Differential responsiveness of the subpopulations that comprise a particular cell type to hypothalamic regulatory factors does not seem to be an exclusive feature of melanotropes, but it increasingly appears as a common attribute among pituitary cell types from different species [42, 43, 44, 45]. The fact that this phenomenon occurs in various pituitary cell types strongly suggests that the differential regulation by the hypothalamus of subpopulations comprising each cell type may play a physiologically relevant role in the control of pituitary function.…”

Section: Discussionmentioning

confidence: 99%

Amphibian Melanotrope Subpopulations Respond Differentially to Hypothalamic Secreto-Inhibitors

et al. 2001

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The melanotrope population of the frog intermediate lobe consists of two subtypes of cells, referred to as high-(HD) and low-density (LD) melanotrope cells, which differ markedly in their basal morphofunctional features as well as their in vitro response to hypothalamic factors, such as the stimulator thyrotropin-releasing hormone (TRH) and the inhibitor dopamine. In this study, we have investigated whether other major hypothalamic regulators of the release of α-melanocyte-stimulating hormone (α-MSH), such as γ-aminobutyric acid (GABA) and neuropeptide Y (NPY), also differentially regulate frog melanotrope subpopulations. Our results show that in LD cells, both factors markedly inhibited proopiomelanocortin (POMC) mRNA accumulation and α-MSH secretion. In contrast, the secretory and biosynthetic activity of HD cells was not modified by GABA. NPY inhibited POMC transcript accumulation and tended to reduce α-MSH secretion in HD cells, yet these effects were less pronounced than those evoked in LD cells. In addition, GABA and NPY inhibited the KCl-induced rise in cytosolic free calcium levels in both subpopulations. Taken together, these results further indicate that frog melanotrope subpopulations are differentially regulated by the hypothalamus and strongly suggest that the intensity of such regulation is directly related to the activity of the cell subset. Thus, the LD subpopulation represents a highly responsive cell subset which is regulated by multiple neuroendocrine factors (TRH, dopamine, GABA and NPY), whereas the hormone storage HD subpopulation shows a moderate response to single stimulatory (TRH) and inhibitory (NPY) inputs.

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“…During the last few years it has been clearly demonstrated that most pituitary tumors are monoclonal in origin with a mutation in a single cell that subsequently undergoes clonal expansion (21,22). This could be an explanation for the variability of the deiodinase activities in the same kind of tumor since endocrine cells which produce the same hormone are a heterogenous population with some cells differing in function and regulation (23). Whether the cytokine expression pattern, known to be changed in pituitary adenoma, or tumor-induced alterations in cellular communication and interaction between hormone producing and folliculo-stellate cells (24 -27) leads to individual tumorspecific changes in the expression of deiodinases remains to be analyzed.…”

Section: Discussionmentioning

confidence: 99%

Expression of 5'-deiodinase enzymes in normal pituitaries and in various human pituitary adenomas

Baur¹,

Buchfelder²,

Köhrle³

2002

European Journal of Endocrinology

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Objective: Local 5 0 -deiodination of L-thyroxine (T 4 ) to active thyroid hormone 3,3 0 ,5-tri-iodothyronine (T 3 ) catalyzed by the two 5 0 -deiodinase enzymes (D1 and D2) regulates various T 3 -dependent functions in the anterior pituitary and has been well studied in rodents. Only limited information about deiodinase expression and its cellular distribution in human anterior pituitaries is available. Design: We examined 5 0 -deiodinase enzyme activities in pituitary adenomas (18 non-functioning, seven TSH-producing, one GH-and TSH-producing, five GH-producing, eight prolactin (PRL)-producing, two adenomas each from patients with Cushing's disease and Nelson's syndrome) and three normal anterior pituitaries. Methods: Activities were measured as release of 125 I 2 from tyrosyl-ring labeled reverse T 3 with or without propylthiouracil, a potent inhibitor of D1 which does not influence D2 activities. Results: Most of the adenomas and normal tissues expressed both isoenzymes, with D2 activity higher than D1. In a few tissues D1 activity was higher than D2 and some tissues did not express D1 activity at all. Highest activities of both enzymes were found in TSH-and PRL-producing adenomas but absolute activities and the D1/D2 ratio were variable in the same kind of tumor in different patients. Conclusion:The finding that all examined tissues expressed 5 0 -deiodinase activity, most of them expressing both isoenzymes, implies that both enzymes are still active in tumors and that local deiodination is important for the function and feedback regulation of human anterior pituitary.

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Ain't misbehavin': reflections on the functional differences among anterior pituitary cells

Cited by 7 publications

References 39 publications

Cushing's disease: a comparison of pituitary corticotroph microadenomas and macroadenomas

Cushing's disease: a comparison of pituitary corticotroph microadenomas and macroadenomas

Amphibian Melanotrope Subpopulations Respond Differentially to Hypothalamic Secreto-Inhibitors

Expression of 5'-deiodinase enzymes in normal pituitaries and in various human pituitary adenomas

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