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

OBJECTIVE: Local 5'-deiodination of l-thyroxine (T(4)) to active thyroid hormone 3,3',5-tri-iodothyronine (T(3)) catalyzed by the two 5'-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'-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(-) 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'-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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Novel neuroanatomical pathways for thyroid hormone action in the human anterior pituitary

Acta Endocrinologica ◽

10.1530/eje.1.02111 ◽

2006 ◽

Vol 154 (3) ◽

pp. 491-500 ◽

Cited By ~ 46

Author(s):

Anneke Alkemade ◽

Edith C Friesema ◽

George G Kuiper ◽

Wilmar M Wiersinga ◽

Dick F Swaab ◽

...

Keyword(s):

Thyroid Hormone ◽

Mhc Class Ii ◽

Anterior Pituitary ◽

Thyroid Hormone Receptor ◽

Human Leukocyte ◽

Cell Types ◽

Human Pituitary ◽

Double Labeling ◽

Tsh Secretion ◽

Human Anterior Pituitary

Objective: An increasing number of proteins appear to be involved in thyroid hormone feedback action at the level of the anterior pituitary, but the cell types expressing these proteins are largely unknown. The aim of the present study was to identify cell types in the human anterior pituitary that express type II and type III deiodinase (D2 and D3), the recently described thyroid hormone transporter (MCT8) and thyroid hormone receptor (TR) isoforms by means of double-labeling immunocytochemistry. Results: We found TR isoforms to be expressed most prominently in gonadotropes and – although to a lesser extent – in thyrotropes, corticotropes, lactotropes and somatotropes. D3 staining showed a distribution pattern that was remarkably similar. By contrast, D2 immunoreactivity was observed exclusively in folliculostellate (FS) cells showing coexpression with human leukocyte antigen (HLA), a marker of major histocompatibility complex (MHC)-class II. MCT8 immunostaining was present in FS cells without HLA coexpression. Conclusions: From these results, we propose a novel neuroanatomical model for thyroid hormone feedback on the human pituitary, with a central role for FS cells in thyroid hormone activation, which thus play an important role in the suppression of TSH secretion by circulating thyroxine (T4).

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Dispersed Human Anterior Pituitary Adenomas Preferentially Attach to Poly-L-Lysine Coated Wells

Clinical Science ◽

10.1042/cs081029pc ◽

1991 ◽

Vol 81 (s25) ◽

pp. 29P-30P

Author(s):

SL Atkin ◽

AM Landolt ◽

RV Jeffreys ◽

White MC

Keyword(s):

Pituitary Adenomas ◽

Anterior Pituitary ◽

Human Anterior Pituitary

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Thyrotrophin receptor protein expression in normal and adenomatous human pituitary

Journal of Endocrinology ◽

10.1677/joe.0.1670007 ◽

2000 ◽

Vol 167 (1) ◽

pp. 7-13 ◽

Cited By ~ 21

Author(s):

M Theodoropoulou ◽

T Arzberger ◽

Y Gruebler ◽

Z Korali ◽

P Mortini ◽

...

Keyword(s):

Protein Expression ◽

Pituitary Adenomas ◽

Anterior Pituitary ◽

Preliminary Evidence ◽

Positive Control ◽

Negative Control ◽

Receptor Protein ◽

Human Pituitary ◽

Thyrotrophin Releasing Hormone ◽

Regulatory Pathways

Thyrotrophin (TSH) synthesis and secretion is under the positive control of thyrotrophin releasing hormone and under the negative control of the thyroid hormones. However, it is hypothesised that TSH has a direct effect on the regulation of its own synthesis through an intrapituitary loop mediated by pituitary TSH receptors (TSH-R). The aim of this investigation was to study the expression of TSH-R in normal human pituitary at mRNA and protein levels, and to compare the pattern of protein expression between different pituitary adenomas. Using RT-PCR we were able to detect TSH-R mRNA in the normal pituitary, and immunohistochemical studies showed TSH-R protein expression in distinct areas of the anterior pituitary. Double immunostaining with antibodies against each of the intrapituitary hormones and S100 revealed that TSH-R protein is present in thyrotrophs and folliculostellate cells. Examination of 58 pituitary adenomas, including two clinically active and two clinically inactive thyrotroph adenomas, revealed TSH-R immunopositivity in only the two clinically inactive thyrotroph adenomas. This study shows, for the first time, the presence of TSH-R protein in the normal anterior pituitary and in a subset of thyrotroph adenomas. The expression of TSH-R in the thyrotroph and folliculostellate cell subpopulations provides preliminary evidence of a role for TSH in autocrine and paracrine regulatory pathways within the anterior pituitary gland.

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A STUDY OF PROLACTIN-LIKE ACTIVITY IN INDIVIDUAL HUMAN PITUITARY GLANDS

Journal of Endocrinology ◽

10.1677/joe.0.0480639 ◽

1970 ◽

Vol 48 (4) ◽

pp. 639-647 ◽

Cited By ~ 3

Author(s):

PATRICIA M. NICHOLSON

Keyword(s):

Growth Hormone ◽

Gel Electrophoresis ◽

Anterior Pituitary ◽

Post Partum ◽

Human Pituitary ◽

Lactating Women ◽

Pituitary Glands ◽

Human Anterior Pituitary ◽

Pituitary Prolactin ◽

Individual Human

SUMMARY Polyacrylamide disc gel electrophoresis of aqueous extracts of individual human anterior pituitary glands failed to identify a protein with lactogenic activity which was characteristic of pregnancy and the post-partum period. Lactogenic activity, determined by a semi-quantitative rabbit mammary gland organ culture assay, was largely associated with the growth hormone fraction. The total prolactin activity of individual anterior pituitary glands was determined by a 'local' intradermal pigeon crop sac method. The glands from pregnant and parturient women did not contain a higher concentration of prolactin than those of men or non-pregnant non-lactating women. These results do not provide any evidence for the existence of a human pituitary prolactin distinct from growth hormone. Reasons for this are discussed.

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Interactions between normal and tumoral tissues at the boundary of human anterior pituitary adenomas

Virchows Archiv ◽

10.1007/bf00197396 ◽

1994 ◽

Vol 424 (1) ◽

Cited By ~ 24

Author(s):

M.R. Farnoud ◽

F. Peillon ◽

J.Y. Li ◽

M. Kujas ◽

J. Racadot ◽

...

Keyword(s):

Pituitary Adenomas ◽

Anterior Pituitary ◽

Human Anterior Pituitary

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Differential Regulation of Proopiomelanocortin and Pituitary-Restricted Transcription Factor (TPIT), a New Marker of Normal and Adenomatous Human Corticotrophs

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2002-021934 ◽

2003 ◽

Vol 88 (7) ◽

pp. 3050-3056 ◽

Cited By ~ 40

Author(s):

Sophie Vallette-Kasic ◽

Dominique Figarella-Branger ◽

Michel Grino ◽

Anne-Marie Pulichino ◽

Henry Dufour ◽

...

Keyword(s):

Transcription Factor ◽

In Situ Hybridization ◽

Pituitary Adenomas ◽

Experimental Models ◽

Pituitary Cells ◽

Human Pituitary ◽

T Box ◽

Normal Human ◽

Human Anterior Pituitary

Since the identification of the pituitary-restricted transcription factor Tpit, a novel T-box factor that is only present in mouse in the two pituitary proopiomelanocortin (POMC)-expressing lineages, no information was available on its pattern of expression in human pituitary. We investigated by immunohistochemistry and in situ hybridization the expression of TPIT in normal human anterior pituitary tissue and in several types of human pituitary adenomas (n = 52). TPIT expression was restricted to the nucleus of normal or adenomatous human corticotroph cells. No specific TPIT immunostaining was detectable in all prolactin (PRL)-, GH-, or gonadotropin-secreting adenomas. In situ hybridization studies demonstrated that TPIT transcripts were coexpressed with POMC mRNA in both secreting and silent corticotroph adenomas, and in normal corticotrophs, whereas TPIT mRNA was not detectable in other types of pituitary adenomas. Unlike POMC, TPIT was not up-regulated by adrenalectomy in rats and did not seem down-regulated in the normal pituitary adjacent to human corticotroph microadenomas. TPIT is the only currently known transcription factor selectively expressed in human normal and adenomatous corticotrophs. In human and experimental models, TPIT and its target gene POMC were thus differentially regulated by glucocorticoids. Moreover, TPIT represents a new marker of POMC-expressing pituitary cells.

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17β-Hydroxysteroid Dehydrogenase Type 1, 2, 3, and 4 Expression and Enzyme Activity in Human Anterior Pituitary Adenomas

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.84.4.5619 ◽

1999 ◽

Vol 84 (4) ◽

pp. 1340-1345

Author(s):

V. L. Green ◽

V. Speirs ◽

A. M. Landolt ◽

P. M. Foy ◽

S. L. Atkin

Keyword(s):

Gene Expression ◽

Enzyme Activity ◽

Pituitary Adenomas ◽

Anterior Pituitary ◽

Estrogenic Activity ◽

Hydroxysteroid Dehydrogenase ◽

Messenger Ribonucleic Acid ◽

Human Anterior Pituitary

17β-Hydroxysteroid dehydrogenase (17βHSD) isoforms reversibly catalyze the final step in the formation of estradiol (E2) from estrone (E1) and the formation of testosterone from androstenedione. We have investigated 17βHSD type 1, 2, 3, and 4 gene expression and 17βHSD estrogenic activity in human anterior pituitary adenomas. 17βHSD messenger ribonucleic acid (mRNA) expression was studied by RT-PCR in 42 pituitary tumors and 3 normal pituitaries, 17βHSD activity was studied in 11 tumors and 17βHSD type 1 was immunolocalized in vitro in 6 tumors. 17βHSD type 1 gene expression was detected in 34 of 42 adenomas in all tumor subtypes; 17βHSD type 2 mRNA was detected in 18 of 42 adenomas, but not in prolactinomas; 17βHSD type 3 mRNA was detected in 12 of 42 adenomas, but not in corticotropinomas; 17βHSD type 4 was expressed in 20 of 42 adenomas by all adenoma subtypes. Reversible 17βHSD activity was found in 9 of 11 adenomas, and 17βHSD type 1 immunopositivity was cytoplasmically distributed in all 6 adenomas in vitro. All 4 17βHSD isoforms are variably expressed in human anterior pituitary adenomas, which also show 17βHSD enzyme activity, suggesting that 17βHSD may play an important role in regulating the local cellular levels of estradiol.

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Basic fibroblastic growth factor stimulates prolactin secretion from human anterior pituitary adenomas without affecting adenoma cell proliferation

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.77.3.831 ◽

1993 ◽

Vol 77 (3) ◽

pp. 831-837 ◽

Cited By ~ 6

Author(s):

S. L. Atkin

Keyword(s):

Cell Proliferation ◽

Growth Factor ◽

Pituitary Adenomas ◽

Anterior Pituitary ◽

Prolactin Secretion ◽

Adenoma Cell ◽

Human Anterior Pituitary ◽

Basic Fibroblastic Growth Factor

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Ontogeny of pituitary thyrotrophs and regulation by endogenous thyroid hormone feedback in the chick embryo

Journal of Endocrinology ◽

10.1677/joe.1.05944 ◽

2005 ◽

Vol 184 (2) ◽

pp. 407-416 ◽

Cited By ~ 20

Author(s):

Michael Muchow ◽

Ioannis Bossis ◽

Tom E Porter

Keyword(s):

Thyroid Hormone ◽

Thyroid Hormones ◽

Anterior Pituitary ◽

Feedback Regulation ◽

Thyroid Stimulating Hormone ◽

Mrna Levels ◽

Hormone Production ◽

Negative Feedback Regulation ◽

Cephalic Lobe ◽

Whole Mount

Increased thyroid hormone production is essential for hatching of the chick and for the increased metabolism necessary for posthatch endothermic life. However, little is known about the ontogeny and distribution of pituitary thyrotrophs during this period or whether pituitary thyroid-stimulating hormone (TSH) production is regulated by endogenous thyroid hormones during chick embryonic development. This study assessed the abundance and location of pituitary thyrotrophs and the regulation of TSHβ peptide and mRNA levels by endogenous thyroid hormones prior to hatching. TSHβ-containing cells were first detected on embryonic day (e) 11, and the thyrotroph population increased to maximum levels on e17 and e19 and then decreased prior to hatching (d1). Thyrotroph distribution within the cephalic lobe of the anterior pituitary was determined on e19 by whole-mount immunocytochemistry for TSHβ peptide and by whole-mount in situ hybridization for TSHβ mRNA. Thyrotroph distribution within the cephalic lobe was heterogeneous among embryos, but most commonly extended from the ventral medial region to the dorsal lateral regions, along the boundary of the cephalic and caudal lobes. Inhibition of endogenous thyroid hormone production with methi-mazole (MMI) decreased plasma thyroxine (T4) levels and increased pituitary TSHβ mRNA levels on e19 and d1. However, control pituitaries contained significantly more TSHβ peptide than MMI-treated pituitaries on e17 and e19, suggesting higher TSH secretion into the blood in MMI-treated groups. We conclude that thyrotroph abundance and TSH production increase prior to hatching, that thyrotrophs are localized heterogenenously within the cephalic lobe of the anterior pituitary at that time, and that TSH gene expression and secretion are under negative feedback regulation from thyroid hormones during this critical period of development.

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