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Pituitary gland in hypothyroidism. Histologic and immunocytologic study.

Primary hypothyroidism is associated with hypertrophy and hyperplasia of thyrotropic cells. In addition, pituitary adenomas that produce thyroid-stimulating hormone occur in both hypothyroidism and hyperthyroidism. The relationship between thyrotropic hyperplasia and adenoma formation is, however, unsettled. We summarize the results of a histologic and immunocytologic study of the pituitary glands of 64 patients with long-standing primary hypothyroidism in an effort to characterize the changes in thyrotropic cells as related to the duration and severity of disease, to therapy, and to the development of thyrotropic adenomas. Diffuse and nodular thyrotropic cell hyperplasia was noted in 69% and 25% of glands, respectively. A crude correlation was observed between the degree of thyrotropic cell hyperplasia and the relative lack of thyroid hormone replacement therapy. In 12% of glands, tumorlet formation was observed, perhaps representing an intermediate stage between nodular hyperplasia and the development of microadenoma. Twelve adenomas were noted, five of which contained thyroid-stimulating hormone immuno-reactive cells. Although thyroid hormone deficiency seemed to selectively affect thyrotropic cells, lactotropic hyperplasia was observed in 20% of patients; the mechanism accounting for prolactin cell hyperplasia remains obscure.

Adenoma↗

[Imaging of tumors of the pituitary gland].

Macrotumors of the sella region usually involve the suprasellar and less commonly the parasellar space. The suprasellar extension of pituitary adenoma, meningeoma, craniopharyngioma, and hypothalamic or chiasmatic glioma count for the most frequent neoplastic entities. In macroadenomas of the pituitary gland invasion of parasellar spaces may occur in 6-10%. Imaging techniques are directed to increase the likelihood of surgical cure and to detect aggressive tumour invasion into surrounding tissues. A dedicated classification basing on indirect MRI signs of tumour extension has been established. With high-resolution high-field (3T) MRI the sella region may be displayed to provide better information compared to lower field strengths.

Adenoma↗

Hydropic degeneration of the anterior pituitary gland (adenohypophysis) in uremic rats.

We observed hydropic degeneration of the anterior pituitary in rats made uremic by nephrotoxic chemicals, especially when the uremic rats were given a pure carbohydrate diet beforehand. The hydropic degeneration caused loss of nuclear and cytoplasmic content of many or most anterior pituitary cells. It was readily visible in paraffin sections by light microscopy. It was exaggerated when water was injected after the nephrotoxin and it was greatly reduced if saline was injected after the nephrotoxin. Low serum sodium levels in affected rats and the response to saline injection suggested that the mechanism for development of hydropic degeneration of the anterior pituitary gland involved hyponatremia. Depletion of total body sodium probably accounts for the enhancement of hydropic degeneration by the pure carbohydrate diet. Morphologic lesions of the anterior pituitary related to hyponatremia and uremia have not been described previously.

Animals↗

Involvement of the corticotropin-releasing factor (CRF) type 2 receptor in CRF-induced thyrotropin release by the amphibian pituitary gland.

Corticotropin-releasing factor (CRF) is considered to be a main adrenocorticotropin-releasing factor in vertebrates. In non-mammalian species, CRF and related peptides cause the release of thyroid-stimulating hormone (TSH) from the anterior pituitary. The actions of CRF peptides are mediated by two G protein coupled receptors (CRF1 and CRF2) that have different ligand specificities. Using ligands that bind preferentially or selectively to the CRF2 we tested the hypothesis that TSH release by the amphibian pituitary gland is mediated by the CRF2. Injection of frog CRF, urocortin 1 or the CRF2-specific ligand urocortin 3 all produced significant, acute increases (by 2 h) in plasma thyroxine concentration in prometamorphic tadpoles. Chronic injections of CRF peptides accelerated tadpole metamorphosis, and the peptides with the highest affinity for the CRF2 (urocortin 1 and sauvagine) had the greatest potency. Ligands selective for the CRF2 (frog urocortin 3, mouse urocortins 2 and 3) all accelerated tadpole metamorphosis. We then tested frog urocortins 1 and 3, mouse urocortin 2 and sauvagine for their TSH-releasing activity using dispersed frog anterior pituitary cells in culture. All of the peptides tested markedly enhanced the release of TSH. Secretagogue-induced TSH release was completely blocked by the general CRF receptor antagonist astressin or the CRF2-specific antagonist antisauvagine-30. Conversely, the type 1 CRF receptor-specific antagonist antalarmin had no effect on TSH secretion. Our results support the hypothesis that CRF-induced TSH release by the amphibian pituitary gland is mediated by the CRF2.

Analysis of Variance↗

Effect of substance P on thyrotropin secretion from the pituitary gland in the rat.

The role of substance P (SP) on thyrotropin (TSH) secretion was investigated in ovariectomized (OVX) female, estrogen-primed OVX, and normal male rats. Third ventricular administration of SP induced a significant increase in plasma TSH levels when compared to control animals in E-primed OVX rats (p less than 0.001). The plasma TSH levels increased in a dose-related manner and reached maximum levels at 10 min after injection. In contrast, intraventricularly injected SP failed to alter plasma TSH levels in both OVX rats and normal male rats. Intravenous administration of SP dramatically stimulated TSH release in E-primed OVX rats (p less than 0.001), whereas SP had no effect on the release of TSH when injected in OVX rats and normal male rats. To investigate any direct action of SP on TSH release from the anterior pituitary gland, synthetic SP was incubated with dispersed anterior pituitary cells harvested from E-primed OVX rats and normal male rats. SP, in the dose range between 10(-8) M and 10(-6) M, failed to alter the release of TSH into the culture medium in vitro. These findings indicate that SP has a stimulatory role in the control of TSH release by an action on the hypothalamus but only in estrogen-primed rats.

Animals↗

H7-resistant protein kinase C substrates in two-dimensional gels of proestrous rat anterior pituitary gland.

The presence of Ca(2+)-dependent and -independent protein kinase C (PKC) activities which were stimulated by phorbol-12,13-dibutyrate (PDBu) and sensitive to the kinase inhibitor staurosporine (IC50 values approx. 100 nM) was demonstrated in proestrous rat anterior pituitary gland. These PDBu-induced activities were completely abolished by the PKC-specific inhibitors Ro31-8220 and GF109203X (3 microM). The Ca(2+)-independent activity was more resistant (IC50 = 61 microM) to the kinase inhibitor H7 than the Ca(2+)-dependent activity (IC50 approx. 20 microM), however, this (unusual) resistance to H7 was not observed in the brain regions, hypothalamus and hippocampus. Possible substrates for the Ca(2+)-independent PKC in anterior pituitary were identified by two-dimensional gel electrophoresis and autoradiography following incubation in vitro with [32P]phosphate and 300 nM PDBu +/- 300 nM staurosporine or 30 microM H7. The phosphorylation of six proteins (16, 16, 25, 36, 65 and 69 kDa) was found to be stimulated by PDBu and inhibited by staurosporine, but not H7, in whole tissue, and another two such phosphorylated proteins (each 76 kDa) were observed in microsomal subcellular fractions. These phosphoproteins may be substrates for an H7-resistant PKC isoform previously shown to mediate a number of cellular responses in rat anterior pituitary gland.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Persistent high MR signal of the posterior pituitary gland in central diabetes insipidus.

We describe three cases of central diabetes insipidus, each with a different pathogenesis, in which unexpected hyperintensity of the posterior pituitary gland was seen on T1-weighted MR images obtained at the time of presentation. In the first case (idiopathic), the posterior pituitary signal persisted more than 10 years; in the second case (Langerhans cell histiocytosis), the signal disappeared within 3 months, despite early specific chemotherapy with etoposide; and in the third case (transient), the posterior signal disappeared within 1 year, but it was documented at the time of spontaneous reversal of polyuria and polydipsia.

Adolescent↗

The anterior pituitary gland: lessons from livestock.

There has been extensive research of the anterior pituitary gland of livestock and poultry due to the economic (agricultural) importance of physiological processes controlled by it including reproduction, growth, lactation and stress. Moreover, farm animals can be biomedical models or useful in evolutionary/ecological research. There are for multiple sites of control of the secretion of anterior pituitary hormones. These include the potential for independent control of proliferation, differentiation, de-differentiation and/or inter-conversion cell death, expression and translation, post-translational modification (potentially generating multiple isoforms with potentially different biological activities), release with or without a specific binding protein and intra-cellular catabolism (proteolysis) of pituitary hormones. Multiple hypothalamic hypophysiotropic peptides (which may also be produced peripherally, e.g. ghrelin) influence the secretion of the anterior pituitary hormones. There is also feedback for hormones from the target endocrine glands. These control mechanisms show broadly a consistency across species and life stages; however, there are some marked differences. Examples from growth hormone, prolactin, follicle stimulating hormone and luteinizing hormone will be considered. In addition, attention will be focused on areas that have been neglected including the role of stellate cells, multiple sub-types of the major adenohypophyseal cells, functional zonation within the anterior pituitary and the role of multiple secretagogues for single hormones.

Animals↗

Feedback effect of oestrogen on luteinizing hormone secretion by the rat pituitary gland.

Ovariectomized rats with neural deafferentation at the level of the posterior border of the anterior hypothalamic area (AC rats) were used to re-evaluate the direct feedback effect of oestrogen on the regulation of LH secretion by the pituitary gland. Synthetic LH releasing hormone (LH-RH; 300 ng/kg), injected at 30 min intervals into AC rats with undetectable basal LH, induced pulsatile increase of serum LH concentrations. Oestradiol-7Beta (5 micrograms), administered i.v. just before the first LH-RH injection, significantly decreased the LH response to a second injection of LH-RH given 30 min later and to subsequent injections. Maximal inhibition was 58%. Oestradiol 17 beta (5 micrograms) given i.v. to control ovariectomized rats decreased serum LH concentrations 40 min after administration; the maximum reduction being 52%. An s.c. injection of oestradiol benzoate (5 micrograms) increased pituitary responsiveness to LH-RH by the next day in AC rats but decreased serum LH levels in control ovariectomized rats. These results indicate that acute inhibitory and chronic facilitatory effects of oestrogen on LH secretion are exerted at the pituitary gland, without a change in LH-RH secretion. The prolonged inhibitory effect of oestrogen is at the level of the hypothalamus and causes a reduction in LH-RH secretion.

Animals↗

Postoperative anosmia after removal of pituitary gland adenomas using the pterional approach.

There have been several studies on anosmia following operations on anterior circulation aneurysms, but no similar study has yet been reported on pituitary gland adenomas which required the transcranial approach. In this study, 38 cases with pituitary gland adenomas, for whom the pterional approach was employed, were observed retrospectively from the point of view of postoperative olfactory nerve function. In the postoperative period only one case complained of impaired sense of smell on the operated side. Eight cases objectively showed olfactory nerve dysfunctions. The olfactory nerve function could be preserved at a relatively high rate of 79 per cent. This high rate, we think, resulted from the microtechnique employed as well as the relatively cautious frontal retraction which was less than 1.5 cm.

Adenoma↗

Electrical activity from cells in the whole, isolated, intact bovine pituitary gland. I. Changes induced by injection of hypothalamic, pineal and intraglandular colloid material.

Spontaneous electrical activity can be recorded from all lobes of the whole, isolated, intact bovine pituitary gland with subdermal electrodes. The potentials can be modified by injecting either crude hypothalamic, pineal gland or intraglandular colloid material. The pituitary cells yield grossly similar responses to these materials, and it is thought that the materials act through distinctly separate receptors.

Action Potentials↗