TSH Cells Research Articles

Ghrelin Immunexpression in Pituitary Adenomas

Ghrelin, an orexigenic hormone occurs mainly in stomach, and in several tumor types. We investigated ghrelin immunopositivity using the streptavidin‐biotin‐peroxidase complex method in the full spectrum of pituitary adenoma subtypes. Quantification was undertaken by analyzing both the percentage of tumor cells stained for ghrelin and the staining intensity.Cytoplasmic ghrelin immunopositivity was identified in several adenoma subtypes. Not every cell was immunopositive; the intensity of staining differed among cells within the given lesion and among the various tumors. The highest scores were noted in GH adenomas exposed to somatostatin analogues. In decreasing order, lower scores were encountered in ACTH‐producing, silent subtype 1 and 2 adenomas in Cushing disease, silent subtype 3 adenomas, untreated GH adenomas, dopamine agonist‐treated PRL adenomas, gonadotroph adenomas, and ACTH adenomas in Nelson syndrome. No immunoreactivity was found in TSH, untreated PRL‐producing, and null cell adenomas. The high immunoexpression of ghrelin in GH adenomas exposed to somatostatin analogues, may be due to increased ghrelin synthesis or to suppression of its release.

Ghrelin immunoexpression in pituitary adenomas

Ghrelin, an orexigenic hormone, is normally produced mainly in stomach. In addition, it has been demonstrated in gastric carcinoid tumors and less often in other neuroendocrine tumors. We investigated ghrelin expression by immunohistochemistry (streptavidin-biotin-peroxidase complex method) in the full spectrum of resected pituitary adenoma subtypes. Quantification of staining considered both the frequency of ghrelin-reactive tumor cells as well as their staining intensity. Cytoplasmic ghrelin immunopositivity was identified in several adenoma subtypes. Cellular staining varied considerably. In addition, the intensity of cell staining differed within the same tumor and between adenoma subtypes. The highest scores were noted in GH producing adenomas exposed to long-acting somatostatin analogs. In decreasing order, lower scores were encountered in ACTH adenomas in Cushing disease, silent subtype 3 adenomas, untreated GH adenomas, silent corticotroph adenomas of subtypes 1 and 2, dopamine agonist-treated PRL adenomas, ACTH adenomas in Nelson syndrome, and gonadotroph adenomas. No significant immunoreactivity was noted in TSH, untreated PRL, and null cell adenomas. The high immunoexpression of ghrelin in GH adenomas exposed to long-acting somatostatin analogs remains unexplained, but may be due to either increased ghrelin production or to suppression of its release. Based on our findings, it appears that ghrelin immunopositivity does not serve as a biomarker of biologic behavior, prognosis and therapeutic responsiveness in pituitary adenomas.

In vivo and in vitro response to octreotide LAR in a TSH-secreting adenoma: characterization of somatostatin receptor expression and role of subtype 5

Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism and account for less than 2% of pituitary adenomas. Medical therapy with somatostatin analogues (SSAs) effectively reduces TSH secretion in approximately 80% of patients and induces shrinkage in about 45% of tumors. According with previous data, resistance to SSA treatment might be due to heterogeneity in somatostatin receptors (SSTRs) expression. We report the case of TSHoma in a 41-year-old man treated with octreotide LAR that caused a dramatic decrease of TSH and thyroid hormones and tumor shrinkage already after 3 months of pre-surgical therapy. In search of potential molecular determinants of octreotide effectiveness, we measured, in primary cultures from this tumor, SSTR and dopamine D2 receptor (D2R) expression, and octreotide and/or cabergoline effects on TSH secretion and cell proliferation. SSTR5 and D2R expression was higher than SSTR2. Octreotide significantly inhibited TSH secretion more effectively than cabergoline (P<0.001), whereas the combined treatment was comparable with cabergoline alone. Similarly, octreotide resulted more effective than cabergoline on cell proliferation, while the combination did not show any additive or synergistic effects. In conclusion, the significant antisecretive and antiproliferative effect of octreotide in this patient might be related to the high expression of SSTR5, in the presence of SSTR2. After reviewing the literature, indeed, in line with previous observations, we hypothesize that SSTR5/SSTR2 ratio in TSHomas may represent a useful marker in predicting the outcome of therapy with SSAs. The role of D2R should be further explored considering that the presence of D2R can influence SSTRs functionality.

Localization of Carboxyl Ester Lipase in Human Pituitary Gland and Pituitary Adenomas

Carboxyl ester lipase (CEL) is an enzyme that hydrolyzes a wide variety of lipid substrates, including ceramides, which are known to show inhibitory regulation of pituitary hormone secretion in experimental models. Because no studies on CEL expression in human pituitary and pituitary adenomas have been reported in the literature, we investigated CEL expression in 10 normal pituitary glands and 86 well-characterized pituitary adenomas [12 FSH/LH cell, 17 α-subunit/null cell, 6 TSH cell, 21 ACTH cell, 11 prolactin (PRL) cell, and 19 GH cell adenomas] using IHC, immunoelectron microscopy, Western blotting, and quantitative RT-PCR. In normal adenohypophysis, CEL was localized in GH, ACTH, and TSH cells. In adenomas, it was mainly found in functioning GH, ACTH, and TSH tumors, whereas its expression was poor in the corresponding silent adenomas and was lacking in FSH/LH cell, null cell, and PRL cell adenomas. Ultrastructurally, CEL was localized in secretory granules close to their membranes. This is the first study demonstrating CEL expression in normal human pituitary glands and in functioning GH, ACTH, and TSH adenomas. Considering that CEL hydrolyzes ceramides, inactivating their inhibitory function on pituitary hormone secretion, our findings suggest a possible role of CEL in the regulation of hormone secretion in both normal and adenomatous pituitary cells.

Oxidative Stress: A Required Condition for Thyroid Cell Proliferation

Goiter is associated with increased oxidative stress (OS). We studied the effects of an anti-inflammatory agent, 15 deoxy-Delta12,14-prostaglandin J2 (15dPGJ2) and an antioxidant, N-acetylcysteine (NAC), on OS, thyroid function, and goiter expansion in a model of goiter induced by propylthiouracil (PTU) or perchlorate. OS was assessed by the immunodetection of 4-hydroxynonenal, thyroid function by measuring thyroxin (T4) and thyrotropin (TSH) plasma levels and detecting T4-rich thyroglobulin (Tg-I), and goiter expansion by weighing the thyroids and measuring cell proliferation (PCNA and cyclin D1 immunodetection). In both PTU and perchlorate-induced goiters, OS, TSH plasma levels, thyroid weight, and cell proliferation were strongly enhanced, whereas Tg-I expression was negative. All these parameters were reversed by NAC and 15dPGJ2 in PTU-goiters. In perchlorate-goiters, TSH plasma levels remained elevated and Tg-I-negative after NAC or 15dPGJ2 treatment. OS was reduced by NAC, but not by 15dPGJ2. In addition, NAC reduced PCNA and cyclin D1 immunostainings, as well as thyroid weight, whereas 15dPGJ2 influenced neither thyroid weight nor cell proliferation. In conclusion, NAC and 15dPGJ2 overcome PTU- but not perchlorate-induced effects. The retrieval of hormonal synthesis may result from direct chemical interactions between PTU and NAC/15dPGJ2. Although 15dPGJ2 has no effect in perchlorate-goiters, the reduction of OS by NAC is associated with altered goiter development, making OS a required condition for the growth of the thyroid gland.

Cytological study of the hypophysis pars anterior of the Indian emballonurid bat Taphozous kachhensis (Dobson)

The anterior pituitary gland (pars anterior) of the bat Taphozous kachhensis was examined cytochemically by employing several cytochemical staining techniques. Six cell types could be recognized, on the basis of their morphological characteristics and tinctorial properties, viz., two types of non-mucoid (acidophilic) STH and LTH, and three types of mucoid (basophilic) TSH, FSH and LH cells; the sixth, ACTH cells, were amphophilic. The cells are arranged in follicles or acini, separated from each other by a thin layer of connective tissue. The non-mucoid cells are much more concentrated in the postero-lateral and postero-median regions of the pars distalis. ACTH and TSH cells are mostly localised in large numbers in the peripheral region of the pars distalis. FSH cells are concentrated towards the antero-lateral, anterior and median regions. LH cells are distributed throughout the pars anterior but are more abundant towards the posterior and lateral regions. The probable role of these cell types in the physiology of reproduction of this bat is discussed.

Characterization of adherens junction protein expression and localization in pituitary cell networks

Our view of anterior pituitary organization has been altered with the recognition that folliculo-stellate (FS) and somatotroph cell populations form large-scale three-dimensional homotypic networks. This morphological cellular organization may optimize communication within the pituitary gland promoting coordinated pulsatile secretion adapted to physiological needs. The aim of this study was to identify the molecules involved in the formation and potential functional organization and/or signaling within these cell-cell networks. Here, we have focused on one class of cell adhesion molecules, the cadherins, since beta-catenin has been detected in the GH cell network. We have characterized, by qPCR and immunohistochemistry, their cellular expression and distribution. We have also examined whether their expression could be modulated during pituitary tissue remodeling. The mouse anterior pituitary has a restricted and cell-type specific repertoire of cadherin expression: cadherin-11 is exclusively expressed in TSH cells; N-cadherin displays a ubiquitous expression pattern but with different levels of expression between endocrine cell types; E-cadherin is restricted to homotypic contacts between FS cells; while cadherin-18 is expressed both in somatotrophs and FS cells. Thus, each cell type presents a defined combinatorial expression of different subsets of cadherins. This cell-type specific cadherin expression profile emerges early during development and undergoes major changes during postnatal development. These results suggest the existence within the anterior pituitary of cell-cell contact signaling based on a defined pattern of cadherin expression, which may play a crucial role in cellular recognition during the formation and fate of pituitary cell homotypic networks.

Central Ghrelin Affects Pituitary-Thyroid Axis: Histomorphological and Hormonal Study in Rats

Body weight depends on the balance between energy intake and consumption. An interaction between ghrelin and thyroid function has been reported only in pathophysiological states. We examined whether intracerebroventricular (ICV) administration of ghrelin affects the structure and function of the pituitary-thyroid axis in young adult male rats. Ghrelin (0.3 nmol/5 μl PBS) or an equal volume of PBS were injected every 24 h into the lateral cerebral ventricle for 5 days. Two hours after the last treatment the animals were killed, their pituitaries and thyroids excised and prepared for further histological, immunohistochemical and morphometric investigation. Serum TSH levels were measured by RIA, while the total T₄ and T₃ levels were examined by ECLIA. Ghrelin treatment increased pituitary weight (p < 0.05) when compared to the controls, with no effect on the thyroid weight. Smaller, degranulated TSH-immunopositive cells were noticed within the pituitaries of ghrelin-treated animals; their cellular and nuclear volume as well as the relative volume density of thyrotrophs decreased (p < 0.05) in comparison to the control values. The level of serum TSH was reduced (p < 0.05). In the thyroid parenchyma of ghrelin-treated rats, an increased number of hypofunctioning follicles was noticed, characterized by flattened, weakly Tg-immunoreactive epithelium and colloid distension. The relative volume densities of the follicles and colloid increased (p < 0.05), while the thyroid index of activation rate and the serum level of total T₄ decreased (p < 0.05). In conclusion, centrally applied ghrelin modulated the immunohistomorphometric features of pituitary TSH cells and decreased the level of serum TSH, consequently changing thyroid morphology and function, by reducing the T₄ hormone level in the serum.

Histopathological Changed of the Hypophysis in Malnutrition in Elderly Subjects

Major objectives in forensic gerontology are physical and mental disorders during aging, which can be caused by various factors involving nutrition and stress, often accompanied by dysfunction in the neuroendocrine systems including the hypophysis. The objective of the present study was to investigate the histopathological changes in the adenohypophysis in elderly subjects using autopsy materials. Hypophyses with a scaphoid shape (group S: 16 males and 4 females; mean age, 78.6 years) and a normal one (group C: 30 males and 20 females; mean age, 65.2 years) were compared. Incidence of the scaphoid-shaped hypophysis mildly increased with age, being 17% in the elderly over 65 years of age. The weight of the pituitary gland in group S (0.42 +/- 0.1 g) was lower than that of group C (0.65 +/- 0.2 g). The degree of fibrosis was higher in group S (31.6% +/- 5.4%) than in group C (18.3% +/- 6.3%). Immunohistochemical staining showed no significant differences in the proportion of the ACTH cells and the TSH cells between the two groups (p > 0.05). However, there was an increase in the proportion of gonadotrophs, prolactin cells, and S-100-containing cells in group S and a decrease in that of GH cells (p < 0.05). These findings may be associated with reduced anabolic, gonadal and hepatic functions due to malnutrition.

The spatial and temporal expression of delta-like protein 1 in the rat pituitary gland during development

An analysis of secreted proteins by the signal sequence trap method using a cDNA library of the rat pituitary anlage at embryonic days (E) 13.5 revealed the abundant expression of delta-like protein 1 (Dlk1) in the pituitary gland. Dlk1, an epidermal growth factor-like repeat protein in preadipocytes, functions in maintaining the preadipose state. Expression of Dlk1 mRNA in the pituitary at E13.5 and in the adult pituitary was confirmed by in situ hybridization. The expression pattern of Dlk1 during pituitary development was also studied by immunohistochemistry. Dlk1 protein first appeared in Rathke's pouch and the infundibulum at E11.5; as development proceeded, expression became restricted to the pars distalis and pars tuberalis (PT). Dlk1 was expressed in most ACTH cells during the embryonic stages, but its expression was limited to only a few ACTH cells in the adult pituitary. It was also expressed in a small population of TSH, GTH, and PRL cells throughout development, whereas it was present in the cytoplasm of most GH cells at all developmental stages. Similarly, Dlk1 was localized in the cytoplasm of PT cells during development. These findings provide new insights into the mechanism of Dlk1 regarding its regulation of pituitary hormone-secreting cells during development.

Immunohistochemical and Morphometric Study of Pituitary Pars Distalis Thyrotrophs of Male Viscacha (Lagostomus maximus maximus): Seasonal Variations and Effect of Melatonin and Castration

The physiology and behavior of viscacha vary along the year according to the modifications of environmental signals such as the photoperiod length, temperature, rainfall pattern, food composition, and social interactions. The pituitary pars distalis thyrotrophs (TSH cells) of male viscacha were immunohistochemically identified, and the morphometric parameters: percentage of immunopositive area (% IA), cell percentage in pars distalis (% PDC), number of cells per reference area (no. cells/RA), and major cellular and nuclear diameters were analyzed. Three different groups of adult male viscachas were used: (1) captured in their natural habitat during the year, (2) melatonin-administered, and (3) castrated. The thyrotrophs were localized in the ventromedial sector, mainly in the pars distalis cephalic extreme. They were oval or pyramidal in shape, and their immunostaining intensity was heterogeneous. The % IA, % PDC, and no. cells/RA exhibited a significant decrease in June-July (winter, gonadal regression period) in relation to February-March (summer-early autumn, reproductive period), and they were recovered in August-September (later winter-early spring, gonadal recovery period). No morphometric variations of TSH cells were observed in melatonin-treated animals, whereas a decrease of the % IA, % PDC, and no. cells/RA was observed in castrated animals in relation to the intact animals. Our results show TSH cell morphometric variations during the year in agreement with the animal's different physiological conditions during the reproductive cycle, and probably in response to the environmental signals changes. Melatonin does not have a direct effect on the TSH cells. However, castration modifies some thyrotroph morphometric parameters, reinforcing the hypothesis that androgens affect the cells activity.

Dexamethasone treatment during pregnancy influences the number of TSH cells in rat fetuses

Glucocorticoids and thyroid hormones control many aspects of fetal development. Using immunohistochemistry and stereology, in the present study we investigated the effects of dexamethasone (Dx) administration during pregnancy on pituitary TSH cells of 19-day-old fetuses. Doses of 1.0, 0.5, and 0.5 mg Dx/kg bw/day were given to the dams on three consecutive days starting on day 16 of gestation. Administration of Dx to pregnant rats induced a significant decline of fetal TSH cell number per unit of area and their volume density in comparison with the corresponding controls. Our results showed that maternal Dx administration inhibited multiplication of TSH cells in 19-day-old fetuses.

Sexual Maturation Modulates Expression of Nuclear Receptor Types in Laser-Captured Single Cells of the Cichlid (Oreochromis niloticus) Pituitary

The role of steroid/thyroid hormones in the regulation of endocrine cells at the level of the pituitary has remained unclear. Therefore, using single-cell quantitative real-time PCR, we examined absolute amounts of transcripts for nuclear receptors [estrogen receptors (ERs) alpha, beta, and gamma; androgen receptors (ARs) a and b; glucocorticoid receptors (GRs) 1, 2a, and 2b; and thyroid hormone receptors (TRs) alpha1, alpha2, and beta] in pituitary cells of immature (IM) and mature (M) male tilapia, Oreochromis niloticus. In the two reproductive stages, ACTH cells expressed only ERbeta, whereas all other pituitary cell types expressed ERalpha + beta, and a subpopulation coexpressed ARa, ARb, GR1, GR2b, and TRbeta but lacked ERgamma, GR2a, TRalpha1, and TRalpha2. IM males had high percentages of LH cells (IM 46.0% vs. M 10.0%), GH cells (IM 23.3% vs. M 7.9%), and prolactin cells (IM 68.8% vs. M 6.0%) with ERbeta, and TSH cells (IM 19.2% vs. M 0.0%) and MSH cells (IM 25.6% vs. M 0.0%) with ERalpha + TRbeta. A high percentage of FSH cells in IM males expressed ERbeta (IM 46.9% vs. M 18.8%), and FSH cells in M males showed significantly high GR1 transcripts (IM 76.0 +/- 5.0 vs. M 195.0 +/- 10.7 copies per cell; P < 0.05), suggesting that FSH cells are regulated differently in the two reproductive stages. Coexpression of ERalpha + beta in high percentages of cells of the GH family (GH, IM 43.8% vs. M 14.3%; prolactin, IM 8.3% vs. M 59.7%; somatolactin, IM 22.2% vs. M 42.2%) suggests that the expression of both ERs is important for functionality. Thus, differential coexpression of genes for nuclear receptors in subpopulations of pituitary cell types suggests multiple steroid/thyroid hormone regulatory pathways at the level of the pituitary during the two reproductive stages.

Expression of Vesicular Glutamate Transporter-2 in Gonadotrope and Thyrotrope Cells of the Rat Pituitary. Regulation by Estrogen and Thyroid Hormone Status

Immunocytochemical studies of the rat adenohypophysis identified a cell population that exhibits immunoreactivity for type-2 vesicular glutamate transporter (VGLUT2), a marker for glutamatergic neuronal phenotype. The in situ hybridization detection of VGLUT2 mRNA expression in adenohypophysial cells verified that VGLUT2 immunoreactivity is due to local synthesis of authentic VGLUT2. Dual-immunofluorescent studies of the hypophyses from male rats showed the presence of VGLUT2 in high percentages of LH (93.3 +/- 1.3%)-, FSH (44.7 +/- 3.9%)-, and TSH (70.0 +/- 5.6%)-immunoreactive cells and its much lower incidence in cells of the prolactin, GH, and ACTH phenotypes. Quantitative in situ hybridization studies have established that the administration of a single dose of 17-beta-estradiol (20 microg/kg; sc) to ovariectomized rats significantly elevated VGLUT2 mRNA in the adenohypophysis 16 h postinjection. Thyroid hormone dependence of VGLUT2 expression was addressed by the comparison of hybridization signals in animal models of hypo- and hyperthyroidism to those in euthyroid controls. Although hyperthyroidism had no effect on VGLUT2 mRNA, hypothyroidism increased adenohypophysial VGLUT2 mRNA levels. This coincided with a decreased ratio of VGLUT2-immunoreactive TSH cells, regarded as a sign of enhanced secretion. The presence of the glutamate marker VGLUT2 in gonadotrope and thyrotrope cells, and its up-regulation by estrogen or hypothyroidism, address the possibility that endocrine cells of the adenohypophysis may cosecrete glutamate with peptide hormones in an estrogen- and thyroid status-regulated manner. The exact roles of endogenous glutamate observed primarily in gonadotropes and thyrotropes, including its putative involvement in autocrine/paracrine regulatory mechanisms, will require clarification.

Subclinical adenomas in postmortem pituitaries: classification and correlations to clinical data

The aim of this study was to examine pituitary adenomas in a series of postmortem pituitaries by use of modern technologies of immunostaining, to classify the adenomas according to the current WHO classification and to analyse the possible associations to the available clinical data. In this study, pituitaries of 3048 autopsy cases obtained from autopsy series of the years 1991-2004 were examined. A total of 334 pituitary adenomas were found in 316 pituitaries. One hundred and thirty-two sparsely granulated prolactin cell adenomas (39.5%), 75 null cell adenomas (22.5%) and 31 oncocytomas were diagnosed. Forty-six ACTH cell adenomas (13.8%, 27 densely granulated, 19 sparsely granulated) and one adenoma composed of Crooke's cells were detected. Twenty-two gonadotroph cell adenomas (6.6%), seven GH cell adenomas (four sparsely granulated, three densely granulated), one mixed GH cell-PRL cell adenoma, two TSH cell adenomas, five plurihormonal adenoma type I, four plurihormonal adenoma type II and two alpha-subunit-only adenomas were seen. Six adenomas remained unclassified because the tissue was not contained in all sections for immunohistochemistry. Seventeen pituitaries included multiple tumours. The overall tumour size ranged from 0.1 to 20 mm in diameter. Among 76 adenomas (22.7%), which had a tumour size of > or = 3 mm, only three tumours were macroadenomas corresponding to a tumour size of more than 10 mm. The evaluation of the available clinical data showed 99 cases of hypertension, 65 cases of diabetes mellitus, six patients with hyperthyroidism and four with hypothyroidism. No symptoms of adenohypophyseal hormone hypersecretion were reported. The statistical correlations to clinical data were discussed. Adenomas in postmortem pituitaries differ from those in surgical series in proportion of adenoma types and biological behaviour.

Effects of ovariectomy and chronic estradiol administration on pituitary–thyroid axis in adult rats

The effects of ovariectomy (Ovx) and of ovariectomy followed by chronic estradiol dipropionate administration (Ovx EDP) on the structure and function of the pituitary–thyroid axis were examined in the rat. Pituitary TSH cells and thyroid tissue were histologically, immunohistochemically and stereologically investigated. Serum TSH and T 4 levels were determined by RIA. Ovx did not affect pituitary weight, but subsequent treatment with EDP led to its more than two-fold increase ( p < 0.05). After ovariectomy, the cellular volume of pituitary TSH-immunoreactive cells increased by 28%, p < 0.05 compared to sham-operated animals (SO). Treatment of Ovx rats with EDP partially reversed this change. However, the relative volume density of thyrotrophs decreased in comparison to the Ovx and SO groups (by 18% and 23%, p < 0.05, respectively). No statistically significant differences in serum TSH levels were observed between the experimental groups. In thyroid tissue both peripheral and central follicles responded to Ovx and EDP treatments. Compared to SO rats, the relative volume densities of the follicles and colloid were increased (by 14% and 30%, p < 0.05, respectively) in Ovx rats. Chronic EDP treatment of Ovx rats reversed these changes to the pre-ovariectomy state. Hyperplasia of thyroid follicular cells and a significant reduction (by 21%, p < 0.05) of the serum level of T 4 were detected. In conclusion, estradiol deficiency and chronic treatment affected pituitary TSH cells and thyroid tissue. The sum effect of Ovx on the pituitary–thyroid axis was slightly stimulatory. Subsequent EDP treatment decreased thyroid functioning but at the same time preserved serum TSH at the control level.

Subclinical adenomas in postmortem pituitaries: classification and correlations to clinical data

Objective: The aim of this study was to examine pituitaryadenomas in a series of postmortem pituitaries by use of modern technologies of immunostaining, to classify the adenomas according to the current WHO classification and to analyse the possible associations to the available clinical data. Methods: In this study, pituitaries of 3048 autopsy cases obtained from autopsy series of the years 1991‐2004 were examined. Results: A total of 334 pituitary adenomas were found in 316 pituitaries. One hundred and thirty-two sparsely granulated prolactin cell adenomas (39.5%), 75 null cell adenomas (22.5%) and 31 oncocytomas were diagnosed. Forty-six ACTH cell adenomas (13.8%, 27 densely granulated, 19 sparsely granulated) and one adenoma composed of Crooke’s cells were detected. Twenty-two gonadotroph cell adenomas (6.6%), seven GH cell adenomas (four sparsely granulated, three densely granulated), one mixed GH cell‐PRL cell adenoma, two TSH cell adenomas, five plurihormonal adenoma type I, four plurihormonal adenoma type II and two a-subunit-only adenomas were seen. Six adenomas remained unclassified because the tissue was not contained in all sections for immunohistochemistry. Seventeen pituitaries included multiple tumours. The overall tumour size ranged from 0.1 to 20 mm in diameter. Among 76 adenomas (22.7%), which had a tumour size of R3 mm, only three tumours were macroadenomas corresponding to a tumour size of more than 10 mm. The evaluation of the available clinical data showed 99 cases of hypertension, 65 cases of diabetes mellitus, six patients with hyper-thyroidism and four with hypothyroidism. No symptoms of adenohypophyseal hormone hypersecretion were reported. The statistical correlations to clinical data were discussed. Conclusions: Adenomas in postmortem pituitaries differ from those in surgical series in proportion of adenoma types and biological behaviour.

Induction of GH, PRL, and TSHβ mRNA by transfection of Pit-1 in a human pituitary adenoma-derived cell line

The functional development of pituitary cells depends on the expression of a combination of transcription factors and co-factors. Pituitary-specific transcription factor-1 (Pit-1) is required for the expression of growth hormone (GH), prolactin (PRL), and the thyroid-stimulating hormone beta subunit (TSH beta) and acts synergistically with the estrogen receptor (ER) and GATA-binding protein 2 (GATA-2) to induce PRL and TSH beta expression, respectively. The glycoprotein hormone alpha subunit (alpha SU) is the first hormone to be expressed during pituitary development. In addition to being expressed in follicle-stimulating hormone, luteinizing hormone (LH), and TSH cells, alpha SU is reported to co-localize with GH in pituitary cells. These findings have led to the suggestion that the expression of Pit-1 in cells of the alpha SU-based gonadotropin cell lineage might also lead to the expression of GH. In this study, we transfected HP 75 cells (derived from a human non-functioning pituitary adenoma that expressed alpha SU and LH beta) with Pit-1 by using an adenovirus FLAG-Pit-1 construct. Most of the transfected cells expressed GH mRNA, with fewer cells expressing PRL and TSH beta mRNA. The HP 75 cells expressed the genes for ER and GATA-2, thus allowing their expression of GH, PRL, and TSH beta mRNA in response to Pit-1. These results support the hypothesis that GH can be induced in cells that possess an active alpha SU gene and shed light on the basic molecular mechanism that drives the development of GH, PRL, and TSH beta expression in the alpha SU-based gonadotroph lineage.

Developmental changes of Islet-1 and its co-localization with pituitary hormones in the pituitary gland of chick embryo by immunohistochemistry

Although Islet-1 expression in the pituitary gland of early mouse embryo has been previously described, there are no reports concerning the correlation of Islet-1 expression with lineage restrictions in cell types at the later stages of pituitary development. The role of Islet-1 in chickens is also unknown. The purpose of this study was to follow, by using immunohistochemistry, the ontogeny of pituitary Islet-1 and the various cell types that contain Islet-1 throughout chick embryo development. A few Islet-1-immunopositive (Islet-1(+)) cells were first detected in the pituitary primordium in two out of six embryos at embryonic day 5.5 (E5.5), most of the Islet-1(+) cells being ventrally located. As development progressed, many more Islet-1(+) cells were observed throughout the pars distalis. The relative percentage of Islet-1(+) cells amongst the total Rathke's pouch cells was 4.4% at E6.5. This increased significantly, reaching 11.1% by E10.5, followed by no significant change until hatching. Dual immunohistochemistry showed that adrenocorticotrophs, somatotrophs and lactotrophs did not express Islet-1. The cellular types expressing Islet-1 included luteinizing-hormone-positive (LH(+)) gonadotrophs and thyroid-stimulating-hormone-positive (TSH(+)) thyrotrophs. The cells co-expressing LH and Islet-1 were initially detected at E6.5, the proportion of LH(+) cells possessing Islet-1 being about 4%; this increased to 63% at E14.5, followed by no significant changes until hatching. TSH and Islet-1 co-localized cells were first observed at E10.5, with about 37% TSH(+) cell expressing Islet-1; this increased to about 50% by E16.5, after which there was no evident change until hatching. These results suggest that Islet-1 is involved in determining the cell lineages, proliferation, differentiation and maintenance of hormone-secreting functions of pituitary gonadotrophs and thyrotrophs of chick embryo.

Effect of &lt;I&gt;Carica papaya&lt;/I&gt; (paw-paw) seeds ethanolic extract on the pituitary, thyroid and parathyroid glands of male wistar rats

Activity of Carica papaya seeds extract on the pituitary, thyroid and parathyroid glands of rats were investigated. The ethanolic extract of C. papaya seeds (50 and 200 mg/kg) was administered orally daily to sexually mature male wistar rats for one and eight weeks. Histology of pituitary and thyroids were prepared. The thyrotrophs (TSH cells) of anterior pituitary showed progressive hypertrophy and degranulation at high dose levels of 200 mg/kg for one and eight weeks respectively. Acidophils somatotrophs (STH cells) and Lactotrophs or prolactin cells (LTH/PRL cells) showed no significant changes in both the experimental groups as compared to control. However, the thyroid glands of rats that were treated with 200 mg/kg extract showed pronounced hypertrophy, hyperplasia and degranulation with many empty follicles devoid of colloid. The parathyroid glands appeared normal. These observations showed possible side-effects of the C. papaya seeds in rats. KEY WORDS: Carica papaya, pituitary, thyroid, prarthyroid, wistar rats. Global Jnl Pure and Applied Sciences Vol.10(4) 2004: 515-517