[Histologic modifications of the endocrine glands of experimental animals treated with paraaminosalicylic acid. 2. Pituitary gland].
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Aminosalicylic Acid↗
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Western blotting for detection of glucocorticoid receptors in the brain and pituitary gland from adrenal intact pigs.
The objectives of the experiments presented here were to develop a method for measuring total glucocorticoid receptors (GRs), in adrenal intact pigs, and to describe the distribution of this receptor in the pituitary gland and selected brain regions. Six male pigs, 14 days of age, were euthanized and the pituitary gland, hypothalamus, prefrontal cortex, and hippocampus were prepared for western blotting using a traditional soluble cytosolic preparation or a whole cell extract preparation. Samples were electrophoresed and immunoblotted using the anti-human GR antibodies #57 and #51. The #57 antibody labeled a doublet at 95 and 87 kDa whereas the #51 GR antibody labeled a single band at 87 kDa. Affinity labeling of GR with [(3)H] dexamethasone mesylate revealed a single band at 87 kDa. Using the soluble cytosolic preparation GR concentrations were highest in the pituitary gland followed by the hypothalamus (P<0. 0001). The amount of GR in the hippocampus and prefrontal cortex was equivalent but lesser (P<0.0001) than that found in the pituitary gland or hypothalamus. With the whole cell extract tissue preparation, GR concentrations were highest (P<0.05) in the prefrontal cortex and hippocampus with lower (P<0.05) levels detected in the hypothalamus. Taken together, these results indicated that the 87-kDa band was the functional GR and that regional distribution of GRs is specific to the type of tissue preparation used. In addition, we have described a procedure (from whole cell extracts) for measuring total GRs in neural and nonneural tissues from adrenal intact pigs.
Adrenal Glands↗
[Metastases of the central nervous system: a prospective study. 3rd Communication: metastases in the pituitary gland, pineal gland, and choroid plexus (author's transl)].
The following frequency of metastases was found among 737 systematically investigated malignant tumors: pituitary gland--26 cases (3.5%); choroid plexus--19 cases (2.6%); pineal gland--13 cases (1.8%). Most of the metastases were only demonstrated by histological examination. Half of the cases with secondary deposits in the pituitary gland (13/26) were single metastases without any other settlements in the central nervous system, whereas about a quarter (3/13) of the pineal metastases were single deposits. Contrary to this, the choroid plexus displayed multiply metastases including carcinosis of the brain and leptomeninges, with the exception of one case (table 5). The age distribution revealed a peak in the old age (6th to 8th decade). Males (n = 35) were more frequently affected than females (n = 23). Carcinomas of the breast, however, showed the highest tendency of all tumors for secondary spread to pituitary gland (12,5%, table 4).
Adult↗
Identification and immunohistochemical localization of various bovine pancreatic trypsin inhibitor-isoforms in bovine pituitary gland.
Three isoinhibitors of bovine pancreatic trypsin inhibitor (BPTI) have been identified and isolated from bovine pituitary gland. The results of the purification process by affinity chromatography on immobilized trypsin, the electrophoretic mobility in non-denaturing conditions, the antiproteolytic activity and the immunochemical reactions indicate that these inhibitors correspond to those previously isolated from bovine spleen and lung. In addition, immunohistochemical experiments show that the isoinhibitors and BPTI are exclusively localized in the mast cells, and not in the endocrine cells, of the pars intermedia and posterior lobe (neurohypophysis) of the pituitary gland. The physiological implications of these findings are discussed.
Animals↗
Factors affecting the susceptibility of the mouse pituitary gland to CD8 T-cell-mediated autoimmunity.
We have previously shown, in a transgenic mouse model, that the pituitary gland is susceptible to CD8 T-cell-mediated autoimmunity, triggered by a cell-specific model autoantigen, resulting in pan-anterior pituitary hypophysitis and dwarfism. In the present study, we now demonstrate that antigen dose, the T-cell precursor frequency, the degree of lymphopenia and the context of target antigen expression, are important parameters determining the time course and extent of the pathological consequences of CD8 T-cell-mediated autoimmunity. Furthermore, our data indicate that the pituitary gland is susceptible to CD8 autoimmunity following an inflammatory insult such as a viral infection. As lymphocytic hypophysitis may be manifest in other autoimmune conditions, and the pituitary gland may be susceptible to T-cell-mediated pathology after immunization with a virus expressing soluble pituitary antigen, it is important to consider that strategies based on vaccination against soluble pituitary gonadotrophins could have other unexpected endocrine consequences.
Animals↗
Annulate lamellae in adenomas of human pituitary glands.
Twelve nontumorous adenohypophyses and 36 various pituitary adenomas, removed by surgery, have been investigated by electron microscopy in order to shed some light on annulate lamellae, primarily on their ultrastructural features, incidence, origin, fate and functional significance. No annulate lamellae were found in the nontumorous adenohypophyses and in 33 pituitary adenomas. They were, however, detected in two adenomas consisting of undifferentiated cells and one adenoma composed of sparsely granulated prolactin cells indicating that these unique membrane configurations cannot be regarded as an exceedingly rare finding and, furthermore, that they may be disclosed not only in undifferentiated but occasionally in highly differentiated cells. Annulate lamellae may arise from endoplasmic reticulum and/or nuclear envelope and consist of arrays of smooth walled double membrane sheets exhibiting regularly spaced interruptions as well as continuities with the endoplasmic reticulum. No relationship was established between annulate lamellae and adenohypophysial secretory activity. Our findings seem to be consistent with the view that annulate lamellae are present in those cells which have the tendency to proliferate.
Adenoma↗
Innervation of the pituitary gland by supraependymal neurons.
Retrograde transport of horseradish peroxidase (HRP) was used to identify supraependymal neurons projecting to the pituitary gland in the hamster. Supraependymal neurons overlying the median eminence were labeled by HRP injections into the neural and intermediate lobes of the pituitary gland; no neurons were labeled following HRP injections confined to the anterior lobe. Supraependymal neurons innervating the pituitary gland may provide a means whereby cerebrospinal fluid-borne substances modulate neuro-intermediate lobe function.
Animals↗
[The study of neuro-adrenolysis of pituitary gland on cancer pain and experimental approach to reveal its mechanism of pain relief].
Neuro-adrenolysis of the pituitary gland by injection of pure alcohol was done to control intractable pain associated with wide-spread cancer, and pituitary functions were measured before and after the injection. Of a series of 46 patients undergoing a total of 57 neuro-adrenolysis of the pituitary gland, 22 (38.6%) of these procedures obtained complete pain relief 22 (38.6%) showed improvement, and the remaining 13 (22.8%) no effect. Hormonal changes of pituitary gland were not same among the cases and there was no correlation between hormonal changes and the occurrence of pain relief. Experimental study was done to investigate the effect of hypophysectomy and intracerebroventricular injection of AVP on pain threshold in rats. The study revealed that hypophysectomy and ventricular injection of AVP dose dependently raised pain threshold and these effects were inhibited by naloxone. These facts suggest that the analgesic effects of hypophysectomy and AVP injection into cerebral ventricle are mediated by beta-endorphin.
Adolescent↗
Alterations induced by clomiphene in the concentrations of oestrogen receptors in the uterus, pituitary gland and hypothalamus of female rats.
Alterations in the concentrations of oestrogen receptors in the uterus, pituitary gland and hypothalamus during the 2 weeks following a single administration of clomiphene citrate (Clomid) to immature, bilaterally ovariectomized rats were investigated. Examination of the uterine wet weight at 1, 7 and 14 days following a single injection of Clomid (100 micrograms, 250 micrograms or 10 mg) indicated significant time- and dose-related increments from a control value of 45 +/- 2 (S.E.M.) mg to a maximum of 123 +/- 3 mg (250 micrograms dose at 14 days). In contrast, a single injection of oestradiol led to a transient increase in the uterine weight on day 1 to 94 +/- 6 mg, but was without effect by days 7 and 14. Analysis of the uterine DNA content 7 and 14 days after treatment with Clomid revealed significant increments from control values of 390 +/- 10 micrograms to a high level of 558 +/- 9 micrograms (10 mg dose at 7 days). There was a transient retention of nuclear oestrogen receptors and rapid replenishment of cytoplasmic oestrogen receptors in less than 24 h in the uteri of animals treated with oestradiol (25 micrograms), but determinations of receptor content in Clomid-treated animals revealed prolonged retention of nuclear receptors and delayed replenishment of cytoplasmic receptors. The duration and extent of retention of nuclear receptors and depletion of cytoplasmic receptors after treatment with Clomid were found to be dose-dependent. Fourteen days after Clomid treatment, levels of oestrogen receptors in nuclei from the uterus were still raised in all treatment groups, whereas replenishment of cytoplasmic receptors was complete in animals treated with the lower doses (100 and 250 micrograms) of Clomid. A single injection of Clomid (250 micrograms) induced similar prolonged retention of nuclear receptors and delayed depletion of cytoplasmic receptors in pituitary tissue. In contrast, changes in the content of oestrogen receptors in the hypothalamus following Clomid treatment were minimal. The limited effect of Clomid on hypothalamic tissue may mean that the pituitary gland is a more important target for this compound than is the hypothalamus. The findings have confirmed earlier reports on the long-term uterotrophic effect of Clomid and have suggested that under these long-term, in-vivo conditions, Clomid acts in the uterus and pituitary gland as a long-acting oestrogen characterized by prolonged retention of oestrogen receptors in the nucleus and delayed, but otherwise effective, replenishment of the oestrogen receptors in the cytoplasm.
Animals↗
Ultrastructure of lipid-containing cells of the anterior pituitary gland of the domestic chicken, Gallus domesticus.
A combination of light and electron microscopy techniques was applied to characterize a luteinizing hormone (LH)-gonadotroph-like cell in the anterior pituitary gland of the adult domestic chicken. This cell type (mean +/- sem, 91 +/- 8 microns2) was larger than typical LH-gonadotrophs (71 +/- 5 microns2, p < 0.01) and seen in pituitary glands from adult males but not those from adult females of the same age. The ultrastructural features of these cells were similar to typical LH-gonadotrophs in the same section, except for the presence of large (1,126 +/- 77 nm diameter), round, or polymorphic electron-dense inclusions (14 +/- 3 per cell) in the cisternae of the endoplasmic reticulum. When resin sections of anterior pituitary gland were stained with the vapours from the fixative osmium tetroxide and a solution of potassium ferricyanide, inclusions were found that appeared to be lipid in nature and were circumscribed by the cisternal membranes of the endoplasmic reticulum. These lipid inclusions were associated occasionally with acid phosphatase and lysosome-like bodies. The cellular pigment, lipofuscin, considered to be a marker of aging, was absent from the anterior pituitary glands from these adult chickens. These observations suggest that the appearance of lipid in LH-gonadotrophs is unlikely to be age-related and an alternative explanation is discussed in relation to a sex difference in the LH response of adult chickens to gonadotrophin-releasing hormone (GnRH).
Acid Phosphatase↗
Estradiol positive feedback on the rat anterior pituitary gland in vitro.
LH surges can be elicited by estradiol (E2). The mechanism could be either by induction of a surge of hypothalamic LH-RH or by directly increasing the responsiveness of the pituitary gland to hypothalamic LH-RH without an LH-RH surge. In order to study the positive feedback of E2 on the anterior pituitary gland, without any possible influence of an LH-RH surge, we utilized long-term in vitro superfusion of the anterior pituitary gland. The E2 concentration was 100 pg/ml and 10(-8) M LH-RH was pulsed every 30 min for 3 min. LH and FSH surge was detected about 21 h after the beginning of the E2 infusion in all three repeated experiments. No surge was detected in any other channels, i.e. control, E2 superfusion alone or LH-RH stimulation alone. This study demonstrates that in the rat the induction of the preovulatory LH peak can be accomplished by a direct effect of E2 upon the anterior pituitary gland, provided it is being stimulated by constant pulses of LH-RH.
Animals↗
Molecular forms of beta-endorphin in the canine pituitary gland.
Acid extracts of anterior and intermediate lobes of the pituitary gland from 4 dogs were fractionated by cation-exchange high-performance liquid chromatography and analyzed by radioimmunoassay, using 2 antibodies: one specific for the midregion of beta-endorphin (beta-end) and the other specific for the N-terminal region of N-acetylated beta-END. Identification of peaks of canine beta-END immunoreactivity was based on the retention times relative to those of synthetic human beta-END standards, with predicted variations attributable to differences in the beta-END amino acid sequences between the 2 species. The canine anterior lobe was found to contain almost exclusively beta-END (1-31). By contrast, the intermediate lobe contained substantial amounts of N-acetylated and C-terminally shortened forms of beta-END. The predominant forms of beta-END in canine intermediate lobe were, in decreasing order of abundance: beta-END (1-27), beta-END (1-31), beta-END (1-26), Ac beta-END (1-27), Ac beta-END (1-26) and Ac beta-END (1-31). Individual beta-END immunoreactivity profiles varied, but the general pattern was consistent among the 4 dogs.
Amino Acid Sequence↗
Ultrastructural differentiation in the nude mouse of transformed cells isolated from the human fetal pituitary gland.
Spontaneously transformed human fetal pituitary cells were isolated from first-passage cultures after 3 to 6 months of long-term maintenance in growth medium containing 15% fetal calf serum. The cells, when injected into nude mice, developed into large tumors in 1 to 2 weeks. Attempts to detect growth hormone, prolactin, follicle-stimulating hormone, luteinizing hormone, or thyroid-stimulating hormone from nude mouse plasma and tumor homogenate by radioimmunoassay were unsuccessful. These hormones could not be demonstrated in tumor cell cytoplasm by immunocytochemistry. Two human fetal pituitary (HFP) cell strains (HFP-T2, HFP-F4) from tissue culture examined at the electron microscopic level were undifferentiated by ultrastructural criteria. However, tumor cells in the nude mice showed signs of fine structural differentiation with well-developed rough endoplasmic reticulum profiles, secretory granules, and intercellular junctions. The tumor cells lost the features of morphological differentiation when returned to tissue culture. These changes could be repeated by alternate passage in nude mouse and tissue culture.
Animals↗
Immunocytochemical localization of the brain-specific S-100 protein in the pituitary gland of adult rat.
The brain-specific S-100 protein was localized at the electron microscopic level in the anterior and posterior pituitary gland of adult rat by indirect immunoperoxidase histology. The protein was found in the stellate cells of the pars distalis and tuberalis, in the marginal cells that line the hypophyseal cleft and in the glia-like cells, the pituicytes, of the neural lobe. The pituicytes, the stellate cells and the marginal cells have in common at least two properties: they all express a brain-specific marker and they are satellite cells to the secretory axons in the neural lobe and of the secretory cells in the adenohypophysis. These properties suggest that the S-100 cells in the pituitary gland are neuroectodermal in origin, possibly glial in nature.
Animals↗
Ontogenetic changes in the expression of estrogen receptor alpha and beta in rat pituitary gland detected by immunohistochemistry.
The physiological effects of estrogen on the pituitary, including cellular proliferation and regulation of hormone synthesis, are mediated by the nuclear estrogen receptor (ER). The purpose of this study was to determine ontogenetic expression of two types of ERs (ERalpha and ERbeta) in the pituitary using specific antibodies, monoclonal antibody (1D5) for ERalpha and polyclonal antibody generated against ERbeta. First, we confirmed the detection of 66- and 55-kDa bands for ERalpha and ERbeta, respectively, in the rat pituitary extract by Western blotting. Then immunostaining with these antibodies was performed using fetal and adult Wistar rat tissues, combined with PRL or LHbeta immunohistochemistry. Intense ERbeta signal was detected throughout the pituitary from day 12 of gestation. However, staining for ERalpha only became detectable from day 17 of gestation. In contrast with the fetal period, nuclei stained for ERalpha were widely distributed in the anterior lobe in the adult rat, whereas ERbeta-positive cells were restricted in the anterior lobe. LHbeta, but not PRL, was colocalized in ERbeta-positive cells. Our results indicated that the major population of ER subtypes in the rat pituitary gland has changed around the day of birth and that the expression of ERbeta may be involved in the differentiation of pituitary cell function to synthesize a specific hormone.
Aging↗
Role of 17 beta-hydroxysteroid dehydrogenase in the modulation of nuclear estradiol receptor binding by progesterone in the rat anterior pituitary gland and the uterus.
Progesterone has been shown to decrease occupied pituitary and uterine nuclear estradiol receptor (E2R) binding in mature and immature estrogen-primed rats. Progesterone has also been shown to stimulate pituitary but not uterine 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) in the rat. The conversion of estradiol to its less active metabolite estrone by 17 beta-HSD and activation of phosphatase are among mechanisms considered to be involved in the reduction of E2R. To determine if 17 beta-HSD stimulation was a mechanism by which progesterone induced nuclear E2R decrease, the synthetic estrogen ethinylestradiol, which is not oxidized by 17 beta-HSD, was used instead of estradiol to prime adult ovariectomized rats. When ethinylestradiol-primed rats received 0.8, 2.0 or 4.0 mg/kg body wt of progesterone 2 h before sacrifice, the total and occupied nuclear E2R accumulation in the anterior pituitary by a subsequent ethinylestradiol injection 1 h later did not show any decrease. This response was different from that observed previously in estradiol-primed animals in which progesterone showed a multiphasic decrease of occupied form of nuclear E2R. However, in the uterus of ethinylestradiol-primed rats, a partial decrease of total and occupied nuclear E2R accumulation was observed in the presence of the three doses of progesterone used. The decrease of uterine nuclear E2R with the three progesterone doses was different from the dose-dependent effect of progesterone observed in the uterus of estradiol-primed rats. Affinity constants of the interaction between [3H]estradiol and the nuclear E2R were similar among groups treated with ethinylestradiol, estradiol and progesterone. These results demonstrate the involvement of 17 beta-HSD in the reduction of anterior pituitary gland E2R by progesterone in the estradiol-treated animals. Furthermore, the mechanism of decrease of E2R by progesterone in the uterus appears to be different from the pituitary gland.
17-Hydroxysteroid Dehydrogenases↗
Receptors and actions of corticotropin-releasing hormone in the primate pituitary gland.
Receptors for CRH were identified in the pituitary gland of several primate species, and their binding characteristics were compared to the ability of CRH to elicit ACTH and cAMP responses in vitro. Autoradiographic analysis of the binding of [125I]Tyr-ovine CRH to frozen pituitary sections revealed CRH receptors in the intermediate and anterior lobes of human, marmoset, and cynomolgus monkey pituitaries. In the cynomolgus monkey, a high density of CRH receptors was present throughout the anterior and intermediate lobes. In the human pituitary, binding was concentrated in the anteromedial portion of the gland, whereas in the marmoset, binding was dense in the intermediate lobe and scattered as clusters throughout the anterior lobe. In membrane-rich fractions from the cynomolgus pituitary binding of [125I]Tyr-ovine CRH was time and temperature dependent, and was specific for CRH-related peptides; specific binding was increased by divalent cations and inhibited by guanyl nucleotides. Scatchard analyses of the binding data revealed a single class of high affinity sites [Kd, 1.93 +/- 0.23 (+/- SEM) nM], with a receptor concentration of 605 +/- 121 fmol/mg. In marmoset pituitary membranes, there were fewer receptors (200 +/- 15 fmol/mg), in agreement with the lower autoradiographic density of CRH binding. In anterior pituitary cell cultures from cynomolgus monkeys, CRH caused a dose-dependent stimulation of cAMP production and ACTH release, with half-maximum effective concentrations in the range of the CRH receptor affinity. Vasopressin and norepinephrine stimulated ACTH release to a much lesser extent, but both potentiated the stimulatory effect of CRH. Angiotensin II had no effect alone, but it also potentiated the effect of CRH. These data demonstrate the presence of CRH receptors in the primate pituitary, with characteristics similar to those in other species in their binding properties, coupling to adenylate cyclase, and functional interactions with other regulators of ACTH secretion that mediate the stimulatory effect of the peptide in the corticotroph.
Adrenocorticotropic Hormone↗
[Interrelationship between the quality of dietary protein and the function of the adrenal cortex. 3. Reactivity of the adrenal cortex and ACTH content of the pituitary gland of rats fed with proteins of various quality].
Trials were performed investigating the reactivity of the adrenals and the ACTH content of the pituitary gland in rats fed proteins of varying quality. A positive correlation was found to exist between the relative weight of the adrenals and the rate of body weight increases as well as between the weight of the pituitary gland and the rate of body weight gains. In either case this process was found to be primarily dependent on the quality of the dietary protein. It was shown that the quality of the dietary protein did not affect the in vitro reactivity of the adrenal glands. The ACTH content of the pituitary gland( determined on the basis of 100 mg of pituitary tissue) did not change considerably.
Adrenal Cortex↗