[In vivo effects of 24R,25-dihydroxyvitamin D3 on kidney alkaline phosphatase and gamma-glutamyltransferase of hypophysectomized rats]. / Effets in vivo de la 24R, 25-dihydroxyvitamine D3 sur la phosphatase alcaline et la gamma-glutamyltransférase du rein de rats hypophysectomisés.

The effects of 24R, 25-dihydroxyvitamin D3 (24, 25 (OH)2 D3) on alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) and acid phosphatase (ACP) activities were investigated on renal cortex of hypophysectomized (Hx) rats. ALP activity was increased by +27, +56 and +60% as compared to controls respectively 3, 6 and 12 h after intraperitoneal administration of the secosteroid (10 pmoles/100 g body weight). Stimulations of GGT activity began only after 6 h (+30%) and 12 h (+ 46%). ACP activity was not modified. In vivo, the two enzymatic inductions in kidneys of Hx rats were higher and longer than those obtained in vitro.

Evidence that growth hormone stimulates protein kinase C activity in isolated rat hepatocytes.

The mechanism of action of growth hormone (GH) is not known, although indirect evidence suggests that protein kinase C (PKC) might play an important role in the insulin-like actions of GH. In this investigation, we directly examined the effects of GH relative to those of insulin on PKC activity in isolated rat hepatocytes. Human GH (10(-7) mol/L) significantly increased the activity of PKC in both cytosolic and particulate fractions. The effect was maximal at 1 minute, disappeared at 5 minutes, and then increased again at 30 minutes in both fractions. At 1 minute, maximal and half-maximal stimulation of PKC activity occurred at hGH concentrations of 10(-7) and 5 x 10(-9) mol/L, respectively. Insulin (10(-7) mol/L) also induced a significant and transient increase in enzyme activity at 2 minutes in cytosolic and particulate fractions; at 30 minutes, PKC activity was decreased in the soluble fraction (-17%) and increased in the particulate fraction (+65%). Measurement of specific [3H]-phorbol dibutyrate (PDBu) binding suggested translocation of PKC from the cytosol to the membrane fraction after 30 minutes of incubation, only after insulin treatment. The early effects of GH and insulin on PKC activity were additive in both the particulate and cytosolic fractions. Although the later effects of GH and insulin on PKC were quite different, both hormones rapidly activated PKC in isolated hepatocytes, suggesting that PKC might be involved in triggering the insulin-like actions of GH.

[In vitro effects of 24R,25-dihydroxyvitamin D3 on alkaline phosphatase and gamma-glutamyltransferase in the kidney of hypophysectomized rats]. / Effets in vitro de la 24R,25-dihydroxyvitamine D3 sur la phosphatase alcaline et la gamma-glutamyltransferase du rein de rat hypophysectomisé.

The effects of 24R,25-dihydroxyvitamin D3 (24,25-(OH)2D3 on alkaline phosphatase (PAL), gamma-glutamyltransferase (GGT) and acid phosphatase (PAC) activities were investigated on renal cortex slices of hypophysectomized rats. Indeed after hypophysectomy renal 24,25-(OH)2D3 production was increased and renal PAL and GGT activities were decreased. After 5h incubation with physiological concentrations (0.1-10 nM) of 24,25-(OH)2D3 significant increases of PAL and GGT activities were produced. The maximum stimulation obtained with 1 nM was +23% for PAL and +26% for GGT as compared to controls. PAC was not modified. The time course of these effects was studied from 45 min to 8 h. In the presence of 24,25-(OH)2D3 (1 nM), delayed (3h) stimulation of PAL and GGT appeared. It reached the maximal value after 6h, +37% for PAL and +30% for GGT and persisted again at 8h. Cycloheximide added to incubation medium with steroid inhibited the stimulating effect on PAL only. Actinomycin D suppressed the induction of both enzymes, indicating that the observed actions of 24,25-(OH)2D3 depend on protein synthesis whose responsible mechanisms were different. These protein synthesis inhibitors did not modified enzymatic activities. Physiological significance of these renal effects is to be clarified.

[In vitro effects of 1,25-dihydroxycholecalciferol on alkaline phosphatase and gamma-glutamyltransferase activity in hypophysectomized rats]. / Effets in vitro du 1,25-dihydroxycholecalciferol sur la phosphatase alcaline et la gamma-glutamyltransferase du rein de rat hypophysectomisé.

Effects in vitro of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) on alkaline phosphatase (PAL), gamma-glutamyltransferase (gamma-GT) and acid phosphatase (PAC) activities were investigated on renal cortex from hypophysectomized rats. In these animals the biosynthesis of 1,25-(OH)2D3 and the specific activities of kidney PAL and gamma-GT were decreased. The course of these effects was determined from 45 min to 8 h. In the presence of 1,25-(OH)2D3 (2 x 10(-6) M) a delayed (5h) but simultaneous stimulation of the three enzymes was observed. It reached a maximum at 6h and disappeared at 8h. The dose-response relation was studied at 6h. In the presence of 1,25-(OH)2D3 (5 x 10(-7) M), the three enzymes were activated. The effect was maximal at 10(-6) M; it was +22% for PAL, +17% and +15% respectively for gamma-GT and PAC compared with controls. Cycloheximide suppressed the induction of PAL but not of gamma-GT activity. The effects of the secosteroid on renal enzymes seems to be a pharmacological more than a physiological one.

[In vitro stimulation of alkaline phosphatase and gamma- glutamyltransferase in the kidney of hypophysectomized rat by the mixture of 1,25 and 24,25 dihydroxycholecalciferols]. / Stimulation in vitro de la phosphatase alcaline et de la gamma-glutamyltransférase du rein de rat hypophysectomisé par le mélange des 1,25 et 24,25 dihydroxycholécalciférols.

The present study was undertaken to investigate the in vitro effects of two cholecalciferol metabolites 1,25(OH)2CC and 24,25(OH)2CC on the renal cortex alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) and acid phosphatase (ACP) activities in hypophysectomized rats. We found that both 1,25-CC and 24,25-CC stimulated ALP and GGT. An additive effect was obtained on ALP and GGT after incubation with one with the other metabolites. When 1,25-CC was used alone, it increased ACP; in presence of 24,25-CC, this stimulating effect disappeared. In the rat, together 1,25-CC and 24,25-CC correct in vitro ALP and GGT activities decreased by hypophysectomy. Physiological signification of these effects remains again unknown.

Thyroidectomy abolishes pulsatile growth hormone secretion without affecting hypothalamic somatostatin.

The effects of thyroid hormone deprivation and of subsequent replacement therapy on growth hormone (GH) secretion were investigated in unrestrained unanesthetized rats. Male rats were thyroparathyroidectomized (TPTX) 5 weeks prior to plasma sampling for GH assay, or to decapitation for evaluation of hypothalamic somatostatin (SRIF) content and in vitro SRIF and GH release. Thyroid hormone deprivation suppressed pulsatile GH secretion as well as GH release induced by clonidine (150 micrograms/kg). Treatment of TPTX rats with small doses of triiodothyronine (T3) restored an episodic pattern of GH secretion, but with lower peak values than controls, as well as the GH response to clonidine. Thyroid deprivation induced a 92-fold decrease in GH release from the pituitary; however, the ratio between GH release and GH content was similar in TPTX and normal rats, and human pancreatic growth hormone-releasing factor (GRF) (3 X 10(-8) M) was still able to stimulate residual GH release by hemipituitaries from TPTX rats in a manner similar to that in euthyroid controls (295 and 254% stimulation, respectively). Thyroid deprivation or T3 replacement did not modify SRIF content in the hypothalamus or other brain structures tested. The capacity of K+ depolarization to release SRIF in vitro from the hypothalamus was not modified by TPTX. These findings indicate that thyroid hormones are necessary to maintain both pulsatile and induced GH secretion in unanesthetized rats. In addition they suggest that impairment of GH secretion in thyroidectomized rats does not depend upon changes in the hypothalamic SRIF regulation of the hormone but could be dependent on a defect in GRF release and/or, most probably, GH synthesis directly at the pituitary level.

[Need of thyroxine in chronic effects of growth hormone (GH) on phosphorus and calcium metabolism of female adult rat (author's transl)]. / Nécessité de la thyroxine pour les effets chroniques de l'hormone de croissance (GH) sur le métabolisme phosphocalcique de la ratte adulte

The object of the present work was to determine the part played by thyroxine (T4) in chronic effects of GH on phosphocalcium metabolism. Therefore, we used hypophysectomized-thyroparathyroidectomized female rats. The results were that: 1. Repeated daily administration of GH to female rats which had been operated on was not followed by the hyperphosphatemia classically observed in normal animals. GH always decreased urinary calcium and phosphorus excretion, indicating a direct renal effect of this hormone, irrespective of blood variations in the ions. 2. Chronic administration of infra-physiological doses of L-thyroxine (0.25 mug/100 g per day) enabled one again to obtain in operated rats the increase of phosphatemia specifically due to GH. 3. With the doses of GH and thyroxine used in these experiments, the blood calcium level of rats which have been operated on decreased. In conclusion, GH intervenes directly in phosphocalcium metabolism and it helps maintain a high phosphatemia. Thyroxine permits this last mentioned effect.

[Early effects of growth hormone on blood and urinary inorganic phosphorus in the rat (author's transl)]. / Effets précoces de l'hormone de croissance sur les phosphates sériques et urinaries du rat

From the kinetic study of the effects of one single growth hormone (GH) injection on the phosphate metabolism, it appears that the influence of GH on the serum phosphate level is biphasic: a decrease is followed by an increase. Conversely GH leads to an early decrease of the urinary phosphate excretion.