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Regulation of renal vitamin D-24-hydroxylase by phosphate: effects of hypophysectomy, growth hormone and insulin-like growth factor I.

Dietary phosphate (Pi) regulates the production of 1,25-dihydroxyvitamin D3. This control is blunted in hypophysectomized (HPX) rats but can be restored by growth hormone (GH) or IGF-I. The regulation of the vitamin D catabolism by Pi, GH and IGF-I is less clear. In the present study, we found that the activity and transcript levels of the catabolic enzyme, vitamin D-24-hydroxylase (24-OHase) were decreased 3- and 5-fold, respectively, during Pi restriction in normal rats, but this effect is greatly reduced in HPX rats. Examination of the serum chemistries revealed that HPX rats on the high Pi diet had lower serum Pi levels than normal rats on this diet, presumably due to the known defective reabsorption of Pi by HPX rats. Treatment of HPX rats, adapted to a 0.6% P diet, with GH (150 micrograms) or IGF-I (80 micrograms) suppressed 24-OHase mRNA levels by 88% and 64%, respectively, by 20 hours and these effects were preceded by decreases in serum Pi. Our findings show that the 24-OHase is regulated by dietary Pi and this control is modulated by hypophysectomy, GH and IGF-I.

Animals↗

Effects of hypophysectomy on coho salmon interrenal: maintenance of steroidogenic pathway and restoration of in vitro responsiveness to adrenocorticotropin after handling.

The role of the pituitary in regulating interrenal activity in coho salmon (Oncorhynchus kisutch) was examined using short- (1 week) or long- (10 week) term hypophysectomized (Hx) animals. In experiments in which Hx animals were injected with ovine growth hormone (oGH), triiodothyronine, or vehicle, plasma cortisol was significantly lower (close to non-detectable, 1 ng/ml) in vehicle-injected or hormone-treated short- and long-term Hx animals compared to vehicle-treated sham-operated (SO animals). Treatment of long-term Hx animals with oGH led to a significant increase in plasma cortisol, in comparison to other Hx groups. Interrenal responsiveness to ACTH or cAMP was not consistently affected by hypophysectomy or hormone treatment. Pregnenolone-supported cortisol production by tissue from Hx groups was at least as great as that by tissue from SO animals; production by tissue from GH-treated, long-term Hx animals was significantly greater than that by tissue from Hx or SO animals. Similar experiments utilizing handling stress (handling and anesthesia) instead of hormone injection as a variable revealed that the response of tissue from Hx animals to ACTH or cAMP was significantly reduced in the absence of handling in comparison with SO animals. However, utilization of pregnenolone as a substrate by tissue from Hx animals was no different from that by tissue from SO animals and was independent of handling. These results indicate that the maintenance of the steroid-biosynthetic pathway is pituitary independent. The decrease in tissue responsiveness to ACTH or cAMP in undisturbed Hx animals may be partially attributable to: (1) the absence of nonpituitary/nonpituitary-mediated factors that are stimulated by handling and which probably upregulate ACTH receptors and mediating systems; and/or (2) to the presence of inhibitory factors which are decreased after handling.

Adrenocorticotropic Hormone↗

Growth hormone inhibits the hypophysectomy-induced expression of galanin in hypothalamic neurons of the toad (Bufo arenarum hensel).

The expression of the neuropeptide galanin was analyzed by immunohistochemistry in magnocellular and preoptic hypothalamic neurons of toads following hypophysectomy (HPX) and pars distalectomy (PDX). There was a marked increase in the galanin-like immunoreactive expression in magnocellular hypothalamic cells 3 days after HPX, followed by a decrease to normal levels after 7 days. No changes in the expression of galanin were detected after PDX in these neurons when compared to controls. Moreover, 7 days after HPX or PDX the number of cells expressing galanin was significantly increased in the preoptic area, where numerous intraependymal cells were intensely immunoreactive. The hypophysis grafts into the hind limb in HPX or PDX animals prevented increased galanin-like immunoreactivity in preoptic cells but not in magnocellular neurons. Similarly, PDX toads given growth hormone showed no GAL-LI in the intraependymal preoptic cells. These results suggest the presence of a region regulation of galanin expression in the preoptic area by hypophyseal hormones, in particular growth hormone.

Animals↗

Normal development of cells with somatostatin immunoreactivity in the pancreas and duodenum of the rat fetus and newborn. Effect of hypophysectomy and intrauterine growth retardation.

Immunohistochemistry was employed to study the development of somatostatin-containing cells in the pancreas and duodenum of rat fetuses and of 1-7 day-old newborns. Immunoreactive cells were first detected in the pancreatic islets on day 17 of gestation and in the duodenum on day 18. Somatostatin cells were numerous in the pancreas and gut at term and in early postnatal stages. The development of somatostatin-containing cells in both pancreatic islets and duodenum was not affected by either fetal hypophysectomy on day 16 or intrauterine growth retardation induced by ligature of the main uterine vessels on day 17 of gestation.

Animals↗

Morphological changes in the ultrastructure of the thyroid epithelium of Notophthalmus viridescens after hypophysectomy and TSH- and prolactin stimulation.

In the newt, Notophthalmus viridescens, hypophysectomy results in progressive atrophy of the thyroid cells to the point of irreversible degeneration. After exclusive TSH-stimulation of hypophysectomized newts, increased endocytotic activity of the follicular epithelium is observed. Prolactin stimulation under the same conditions prevents atrophy but does not result in increased cell activity, as expressed by the reduced amount of microvilli and the lack of endocytotic activity. Combined TSH- and prolactin stimulation also results in cell activation, but the activation level of exclusively TSH-stimulated cells is not reached. Although prolactin prevents cellular atrophy and degeneration of the follicular epithelium, it reduces the TSH-induced activation of the thyroid epithelium.

Animals↗

Ultrastructural examination of the regeneration of the rat adenohypophysis after partial hypophysectomy.

Male Wistar rats were partially hypophysectomized and sacrificed at intervals of from 2 days to 1 year following the operation. The resected material was examined under the light microscope and the residual pituitary under the light and electron microscope. Neither regeneration nor an anatomical restoration of the adenohypophysis occurred even one year after partial hypophysectomy. An increased number of small chromophobe stem cells and juvenile chromophil cells were found in the residual pituitary. The amount of mitoses were not significantly increased. The ACTH, FSH and prolactin producing cells demonstrated electron microscopically distinct changes which were interpreted as signs of intensified activity. This can be seen as a "functional regeneration" to maintain vital pituitary function for the organism.

Animals↗

[The transseptal-transsphenoidal approach in hypophysectomy (author's transl)].

The transseptal-transsphenoidal approach in hypophysectomy is more advantageous than all other accesses because the pituitary gland can be removed oppositely. By that way the damage of e.g. the optic nerve or the carotid artery can be avoided. The possiblity of perforation of the nasal septum, deformation of the tip of the nose or rhinitis sicca has only small importance. Moreover the neurosurgeon meets with a great and clear operating area because the anterior wall of the sella turcica can be resected extremely. The transseptal-transsphenoidal approach is simple, distinct and shortens the operation time.

Humans↗

Radioimmunoassay of enkephalins. Regional distribution in rat brain after morphine treatment and hypophysectomy.

Using highly sensitive and highly specific antisera methionine- and leucine-enkephalin levels were determined in various areas of the rat brain. The highest content of both enkephalins was found in the striatum and the hypothalamus, whereas in the hippocampus, the cerebellum and the cortex only a low content was present. The ratio methionine-enkephalin/leucine-enkephalin was about three. Neither acute or chronic morphine treatment nor precipitated morphine withdrawal induced significant changes in enkephalin levels in any brain region. Also hypophysectomy did not affect the enkephalin content of the various brain regions.

Animals↗

Effect of hypophysectomy on cAMP changes in rat adrenal medulla evoked by catecholamines and carbamylcholine.

It was the aim of this study to investigate the mechanisms responsible for changes in 3',5'-cyclic adenosine monophosphate (cAMP) in the rat adrenal medulla occuring after administration of carbamylcholine, histamine, ACTH and various phenylethylamines. Carbamylcholine, ACTH, histamine, noradrenaline and dopamine produced marked (500-900%) increases in adrenal cAMP which were very similar in both adrenal cortex and medulla both with respect to time-course and relative extent. Interestingly isoprenaline and adrenaline did not influence cAMP levels even at excessively high doses. In all cases studied transsection of the splanchnic fibers supplying the adrenals reduced the increase in medullary cAMP by not more than 25--30%, suggesting that cAMP levels in the adrenal medulla are predominantly regulated by non-neuronal mechanisms. This assumption was strongly supported by the observation that hypophysectomy completely abolished the 500--600% increase in cAMP produced by 50 mumol/kg of dopamine and reduced the 700% increase resulting from 4.4 mumol/kg of carbamylcholine to 70%. In spite of the marked increase in cAMP produced by single and repeated doses of dopamine in the adrenal medulla there was no subsequent induction of tyrosine hydroxylase (TH). Moreover carbamylcholine (8.2 mumol/kg) evoked TH induction only in innervated adrenals whereas after denervation, in spite of the large (+ 500%) and prolonged (more than 90 min) increase in cAMP, no TH induction could be observed. It is concluded that adrenal medullary cAMP is predominantly regulated by the pituitary gland via the adrenal cortex and only to a much smaller extent--if at all--by direct cholinergic mechanisms, which are responsible for the initiation of TH induction.

Adrenal Cortex↗

Effects of hypophysectomy, adrenalectomy and (-)-propranolol on ethanol-induced decrease in plasma amino acids.

In previous studies we have demonstrated that an acute dose of ethanol cause an immediate decrease in most plasma amino acids in both man and rat. This effect of ethanol is partly inhibited by the beta-adrenergic antagonist (-)-propranolol, partly by adrenalectomy or hypophysectomy and almost completely by a combination of adrenalectomy with (-)-propranolol. This finding suggests an involvement of both beta-adrenergic mechanisms and steroids from the adrenal cortex in the ethanol-induced decrease in plasma amino acids.

Adrenalectomy↗

Effect of hypophysectomy on the stimulation of liver growth by alpha-hexachlorocyclohexane, phenobarbital, and partial hepatectomy in the rat.

alpha-Hexachlorocyclohexane (alpha-HCH) or phenobarbital (PB) elicit growth and cell multiplication in rat liver. In hypophysectomized rats, alpha-HCH and PB induce an increase in liver mass, but no increase in liver DNA. Hypophysectomy without additional treatment results in a decrease of liver size and RNA, while the DNA content remains unchanged, thereby leading to a relative DNA surplus. 1/3-hepatectomy in hypophysectomized animals leads to a small increase of hepatic DNA only; after 2/3-hepatectomy 75-80% of the original liver DNA are restored. In rats with intact hypophysis losses of liver DNA are known to be restored completely. The findings suggest that the relative DNA surplus in hypophysectomized rats prevents the stimulation of DNA synthesis by weak growth stimuli such as alpha-HCH, PB, and 1/3-hepatectomy. If the relative DNA surplus is eliminated by partial hepatectomy, the inducers do produce DNA multiplication. It is concluded that the induction of liver growth and cell multiplication by alpha-HCH and PB does not require the presence of the hypophysis or one of its hormones.

Animals↗

Influence of transsphenoidal hypophysectomy on visual deficit due to a pituitary tumour.

The effect of transsphenoidal hypophysectomy is presented in 60 patients with visual impairment due to a pituitary adenoma, derived from a total series of 194 patients. The preoperative visual acuity and visual fields were compared with those one year after operation. The visual field loss was estimated using a semi-quantitative method. Seventy-two eyes had diminished visual acuity, and this improved in 45 eyes (63%). Visual field loss was present in 102 eyes and this improved in 71 eyes (70%). Improvement of either visual acuity and/or visual field was found in 84 eyes (78%). In 16 patients (27%) vision became normal after operation. Improvement of the visual acuity was usually accompanied by an improvement in the visual fields.

Adenoma↗

Hypophysectomy exerts a radioprotective effect on frog lens.

Exposure to X-rays usually causes cataracts in frogs. These cataracts are always preceded by misalignment of the structures called meridional rows (MR). When cell division is completely halted by hypophysectomy, however, irradiation no longer disturbs the orientation of the MR. Since the MR are the structures formed as lens epithelial cells differentiate into lens fibres it is reasonable to propose that radiocataractogenesis depends upon a mitosis-driven formation of pathological fibres from epithelial cells that have been rendered abnormal by exposure to X-rays.

Animals↗

Ultrastructural study concerning disintegration of fibrin foam used as filling material after partial hypophysectomy in rats.

After partial hypophysectomy in rats, fibrin foam was implanted in the wound cavity. The fate of the implant was followed over a period of time up to three months by light and electron microscopy. First of all granulocytes appeared, whose granules obviously participated in the fragmentation of the fibrin network. Two days after operation and then in rapidly increasing numbers histiocytes could be found which surrounded the fibrin fibres with pseudopodia and absorbed them. They were broken down intracellularly by the lysosomes. In the wound cavity the gradually increasing number of fibroblasts formed collagen that often lay close to the fibrin fibres. The disintegration of the Fibrospum corresponded largely to that of natural native fibrin even though some could be identified three months after operation. The isolated appearance of foreign giant cells argued in favour of a moderate tuberculin type allergic reaction by the rat.

Animals↗

Effects of hypophysectomy and adrenalectomy on naloxone-induced analgesia.

Experiment 1 demonstrated that pairings of the opiate antagonist, naloxone, with a heated floor came to induce analgesia, as indexed by the latencies with which rats licked their paws. This analgesia appears to be neurally mediated because it is unaffected by either hypophysectomy (experiment 2) or adrenalectomy (experiment 3). However, there was evidence for a pituitary involvement, as its removal potentiated the analgesic effect accruing from naloxone-stressor pairings.

Adrenalectomy↗