Hx Rats Research Articles

Resting metabolism in hypoxia-acclimated rats during acute hypoxic exposure.

In contrast to the decreased metabolism in non-hypoxia-acclimated (CT) rats, acute hypoxia (9.5% O2) did not change the resting metabolism in hypoxia-acclimated (HX: 12% O2 for 2 months) rats at 25 degrees C. After beta-adrenergic blockade, acute hypoxia greatly reduced the resting metabolism in HX rats. The calorigenic response to norepinephrine (0.4 mg . kg-1) during acute hypoxia was, however, identical with that observed in CT rats. These results suggest an enhanced beta-adrenergic stimulation in HX rats during acute-exposure to hypoxia.

Multihormonal regulation of the estrogen receptor in rat liver.

Hepatic estrogen receptors were measured in ovariectomized female rats using isoelectric focusing in polyacrylamide gel. Hypophysectomy or adrenalectomy reduced the receptor level to approximately 10% and 42%, respectively, of the control value. Treatment of hypophysectomized (Hx) rats with dexamethasone alone was without effect. When Hx rats were given a pituitary transplant under the kidney capsule in order to induce liver estrogen receptors, dexamethasone treatment more than doubled the inductive effect of the pituitary transplant. The administration of human GH (hGH) in osmotic minipumps to Hx rats led to an induction of hepatic estrogen receptor levels to 48% of the control value. When hGH infusion was combined with dexamethasone treatment, a complete restoration of the receptor level to that in control rats was seen. When administered in minipumps, ovine PRL (oPRL) and bovine GH (bGH) as well as a combination of oPRL and bGH led to an induction of estrogen receptors in Hx rat livers when dexamethasone treatment was given simultaneously. However, oPRL, bGH, and oPRL plus bGH failed to give a complete restoration of hepatic estrogen receptor levels. It is concluded that the estrogen receptor in rat liver is under multihormonal control and that glucocorticoids in combination with a pituitary factor(s) with similar properties to hGH seem to be responsible for the maintenance of the normal level of the receptor in female rats. Possibly, both GH and PRL are involved in the control of the receptor.

Testicular function of actively immunized male rats with LH releasing hormone (LHRH): a possible role of prolactin on regulation of spermatogenesis.

The effect of testosterone propionate (TP) on the recovery of spermatogenesis was compared in 3 types of experimentally induced gonadotropin-deficient rats; 1. hypophysectomized rats, 2. rats actively immunized to LHRH and 3. hypophysectomized and immunized rats bearing a pituitary isograft. In order to immunize animals to LHRH, deamidated LHRH conjugated with BSA (LHRH-BSA) was injected intradermally to male rats 4 times at 2 week intervals and additional booster injections continued once a month. Anti-LHRH titer was the highest on the 12th week and the titer remained at a relatively high levels thereafter. A remarkable decrease in testicular weight and testosterone production was achieved in 10 weeks associated with a drop in serum LH and FSH levels. In long term immunized rat (LIM rats) which had been immunized for more than 3 months, testicular atrophy advanced to a similar extent to that in long term hypophysectomized rats (HX rats). The administration of TP (1 mg/day) sc for 30 days restored spermatogenesis in LIM rats. The simultaneous administration of anti-LH and -FSH sera in addition to TP did not affect the restoration of spermatogenesis in LIM rats. The same TP treatment in HX rats, however, failed to restore spermatogenesis. Spermatogenesis was reinitiated after TP treatment if immunized-hypophysectomized rats received a pituitary isograft. Though the serum PRL level in LIM rats was one fifth of that in normal rats, a 2.5-fold rise in the PRL level was observed after TP treatment. These results suggest that PRL is involved in the process of spermatogenesis.

The relationship of growth hormone to 1,25-dihydroxyvitamin D 3 in intestinal calcium transport

The effects of 1,25-dihydroxyvitamin D 3 (1,25(OH) 2D 3) and bovine growth hormone (bGH) on intestinal calcium transport have been assessed in vitamin D deficient rats. Calcium transport did not increase after 7 days bGH treatment. A single dose of 1,25(OH) 2D 3 significantly increased calcium transport in the hypophysectomized (Hx) rats treated with bGH but not in the Hx rats who did not receive bGH, unless the dosage of 1,25(OH) 2D 3 was increased to 500 p moles. Even though calcium transport in the Hx rats was stimulated by the high dose of 1,25(OH) 2D 3, this response was less in the Hx than in bGH treated group. These results suggest that growth hormone status may be important in the expression of 1,25-(OH) 2D 3 action on intestinal calcium transport.

Description and partial characterization of thyroid hormone-specific and thyroid hormone-dependent rat liver nuclear proteins.

A fraction of readily elutable rat liver nuclear proteins (nuclear globulins), analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, contains two proteins which reflect the thyroid status of the animal. The larger (n-band) protein is abundant in normal rat nuclei but diminished in hypothyroidism by thyroidectomy or hypophysectomy and restored with T3 treatment. It is also diminished in starvation, during which time T3 treatment of concurrent hypothyroxinemia is ineffective in tis restoration. Refeeding restores the n-band protein in starved normal rats but not in starved thyroidectomized (Tx) rats. GH does not restore this protein in either Tx or hypophysectomized (Hx) rats. The dual requirements of euthyroidism and adequate nutrition imply that the n-band protein is thyroid hormone dependent but not thyroid hormone specific. The smaller of the two nuclear globulins, the t-band protein, is prominent in Tx or Hx rats and is not altered by additional hypometabolic factors (starvation) or by nonthyroid hormone related hypermetabolic stimuli (refeeding or GH treatment of Hx rats). It is reduced in normal or T3-treated Tx or Hx rats regardless of simultaneous hypometabolic states (starvation or nonthyroid hormone-related deficiencies of hypopituitarism) or hypermetabolic states (refeeding, liver regeneration, or hyperthyroidism). The t-band protein thus appears to be inversely thyroid hormone specific in its concentration. Electrophoretic and chromatographic analysis suggest that the n-band protein is a 125,000 mol wt subunit of a 290,000 mol wt holoprotein. The t-band protein is a 70,000 mol wt peptide which exists, in part, as a monomer but largely as a subunit of a protein complex with a mol wt greater than 100,000.

"Short" loop feedback regulation of hypothalamic and brain thyrotropin-releasing hormone content in the rat and dwarf mouse.

In order to determine whether T4, TSH, or both affect hypothalamic TRH content, primary or secondary hypothyroidism was induced in the rat by thyroidectomy (Tx) or hypophysectomy (Hx), respectively. Two weeks later, rats were treated with T4, TSH, or both for 14--16 days. Tx or Hx significantly decreased hypothalamic TRH content, and T4 treatment restored hypothalamic TRH to normal in the Tx but not in the Hx rats. When TSH was administered simultaneously with T4 to Hx rats, hypothalamic TRH content was restored to normal. Whole brain TRH content was not affected by Tx, Hx, or by the various treatment regimens. Similar experiments were performed in Snell dwarf (dw/dw) mice. Hypothalamic TRH content was significantly decreased when compared to normal litter mates (dw/+). As in Hx rats, T4 administration to dw/dw mice for 16 days did not restore hypothalamic TRH content to normal. Brain TRH content was similar in both groups and was not altered by T4 treatment. It is concluded that T4 affects hypothalamic TRH content, but that TSH is required for this T4 effect. Whole brain TRH, on the other hand, is unaffected by any of these alterations in thyroid-pituitary function.

The effect of hypophysectomy on the uterine response to estradiol.

Following estradiol (E2) administration early increases (within 4 h) in uterine wet weight and the synthesis of 2-deoxyglucose-6-phosphate (2-DGP) from 2-deoxyglucose (2-DG) are similar in ovariectomized (OVX) and ovariectomizedhypophysectomized (OVX-HX) rats. Most late uterine responses occurring 24 h after hormone treatment, however, are greatly diminished in OVXHX animals relative to OVX animals. The diminished responses include increases in uterine wet weight, dry weight, RNA content, protein content and the incorporation of thymidine into uterine DNA. These late uterine responses are not diminished in OVXSham HX rats relative to OVX rats. The diminished responses observed in OVX-HX rats are not due to a shift in the dose-response curve for E2, but result from a decrease in the magnitude of the maximum uterine response. These diminished responses are not due to alterations in the content, structure or binding affinity of uterine E2 receptors in OVX-HX rats relative to OVX rats. One late response, the ...

Effect of food deprivation and hypophysectomy on in vitro protein synthesis by membrain-bound and free hepatic ribosomes.

The protein synthetic activities of membrane-bound and free hepatic ribosomes isolated from intact rats fed ad libitum, and normal rats subjected to food restriction to match that of hypophysectomised (Hx) rats were compared to the in vitro protein synthetic capacity of hepatic ribosomes isolated from Hx rats. Hypophysectomy resulted in decreased protein synthetic ability of bound ribosomes, whether protein synthesis was directed by endogenous messenger RNA (mRNA) (p less than 0.05) or by polyuridylic acid (polyU) (p less than 0.01). In contrast, the protein synthetic activity of free hepatic ribosomes from Hx rats was reduced when protein synthesis was directed by endogenous mRNA (p less than 0.05) but, when polyU was substituted as the messenger, the protein synthetic activity of these free ribosomes was equal to that of control rats. On the other hand the effects of food restriction on hepatic ribosomal function could be clearly differentiated from the effects observed following hypophysectomy. Thus, the reduced protein synthetic activity of hepatic bound ribosomes isolated from food restricted normal rats was not demonstrable, when polyU was used to direct protein synthesis. Further, food restriction had no effect on the protein synthetic activity of free hepatic ribosomes, and this was true when protein synthesis was directed by either endogenous or artificial messenger. It is concluded that hypophysectomy reduces the protein synthetic ability of both bound and free hepatic ribosomes, and this change of ribosomal function of Hx rats cannot be attributed to their decreased food intake.

Effect of hypophysectomy on protein synthetic-activity of free and bound hepatic ribosomes from insulin-deficient rats

Acute insulin deficiency in rats results in a decrease in the in vitro protein synthetic activity of isolated hepatic membrane-bound ribosomes and an increase in activity of free ribosomes. These changes are prevented by concomitant insulin treatment and are reversed by the administration of insulin. The current study evaluated the role of the pituitary in the genesis of these changes. The severity of diabetes produced by streptozotocin was less in hypophysectomized (Hx) rats, and in Hx rats receiving hormone replacement, as compared with similarly streptozotocin-treated intact rats. Although acute insulin deficiency in intact rats produced the previously described increase in protein synthetic activity of free hepatic ribosomes and decrease in activity of hepatic bound ribosomes, these changes did not occur in Hx rats, even when Hx rats received replacement doses of thyroxine, ACTH, and growth hormone. Thus, the changes in hepatic protein synthetic activity that occur in rats with acute experimental diabetes mellitus are secondary to the metabolic sequalae of insulin lack and the response of the pituitary gland to insulin deficiency.

Increased serum prolactin induced in hypophysectomized rats bearing ectopic pituitaries.

SummaryA radioimmunassay was developed for quantifying rat prolactin in blood serum, but the assay detected small amounts of immunoreactive prolactin in serum from hypophysectomized (Hx) rats. Prolonged anesthesia of these Hx rats with urethane significantly decreased their serum prolactin values, while prolonged anesthesia with pentobarbital (PB) had no significant effect.Transplantation of pituitary tissue (AP) to the renal capsule of Hx rats elevated serum prolactin, and this effect was produced with as little as I/8 AP. Prolonged PB or urethane anesthesia combined with multiple blood sampling of Hx rats bearing ectopic AP significantly increased serum prolactin. The absence of stable prolactin concentrations an these rats suggests that prolactin release by ectopic AP may still be influenced by hypothalamic hypophysiotrophic hormones in the systemic circulation.

Studies on the effects of growth hormone and thyroxine on proinsulin synthesis and insulin formation in the isolated islets of Langerhans of the rat.

By using pulse-chase and islet-fractionating techniques, proinsulin synthesis and insulin formation in isolated islets from normal and hypophysectomized (Hx) rats have been studied. In both groups of rat islets, proinsulin synthesis took place in the microsomal fraction and its conversion to insulin in the granular fraction (which includes the Golgi complex). The total incorporation of 3H-leucine into proinsulin and insulin in the islets from Hx rats during the 30 min period of pulsing was 48% of the value obtained in the normal islets from control rats. When growth hormone (GH) was added to the incubation medium for islets from Hx rats, a substantial increase (79% of that found in normal islets) in total incorporation of 3H-leucine into proinsulin and insulin was observed. When the incubation mixture was supplemented with thyroxine (THY) along with growth hormone, the conversion of proinsulin to insulin was increased during the pulsing and chasing periods. The enhancement of insulin biosynthesis as a result of both GH and THY was confirmed by straight pulsing experiments. The possible mechanisms for the enhanced effect are discussed.

In vitro stimulation of 14 C-leucine incorporation into protein by growth hormone.

The incorporation of 14C-leucine into protein was measured in liver slices of normal and hypophysectomized (Hx) rats which were incubated for various lengths of time in a modified tissue culture medium. The rate of incorporation in slices of Hx animals was approximately 50% that of normal rats. In the presence of 4 μg/ml growth hormone (GH)/ml of medium, slices derived from normal rats incorporated 25% more labeled precursor into protein than in the absence of hormone. The in vitro addition of GH to slices of Hx rats also stimulated protein synthesis. The specific activity of labeled protein was increased maximally (29%) by the addition of 4 μg GH/ml of medium. GH added at concentrations of 2 and 8 μg/ml enhanced incorporation 15% and 21%, respectively. No effect was observed when GH was present at 0.1 μg/ml medium. Studies in which slices were separated into subcellular fractions revealed that GH increased the specific activity of cytosol protein 48%. These findings indicate that the in vitro addition of...