PubMed Health⌕ Search

Biomedical subjects

L R Forte

Publications and source records attributed to L R Forte.

At least 73 records · Page 4Linked to original sources
PubMed1985

Renal cAMP and 1,25(OH)2D3 synthesis in estrogen-treated chick embryos and hens.

Onset of sexual maturity in female chickens or administration of estrogen to mature males or to juveniles of either sex results in increased parathyroid hormone (PTH)-dependent adenylate cyclase activity and increased 25-hydroxyvitamin D3-1-hydroxylase activity in kidney. The relationship between estrogen-mediated alterations of these two enzyme systems was investigated in embryonic and mature, egg-laying chickens treated in vivo with 17 beta-estradiol (E2). Basal and PTH- and forskolin-stimulated adenylate cyclase activity in kidney plasma membrane preparations was not affected by E2 treatment of 19-day-old chick embryos or of 41-wk-old egg-laying females. High, possibly maximal, levels of catalytic activity in control embryos and hens may have precluded further stimulation by E2. In contrast, E2 significantly enhanced 25-hydroxyvitamin D3-1-hydroxylase activity of embryonic kidney up to 10-fold (P less than 0.005). In mature females, E2 caused cessation of egg laying accompanied by a significant reduction (P less than 0.005) of 25-hydroxyvitamin D3-1-hydroxylase activity. These results indicate that the PTH-dependent adenylate cyclase and the 25-hydroxyvitamin D3-1-hydroxylase systems of avian kidney can be regulated independently and suggest that factors in addition to estrogen are involved in their regulation.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1985

Hypercalcemia in rats bearing growth hormone- and prolactin-secreting transplantable pituitary tumors.

We evaluated the effects of chronic massive elevations of serum GH and PRL on calcium metabolism in rats bearing the MStT/W15 and 7315a transplantable pituitary tumors. MStT/W15 tumor rats manifest elevated serum GH and PRL levels, hypercalcemia, hypercalciuria, and elevated serum levels of PTH and 1,25-dihydroxyvitamin D. The hypercalcemia was not reversed by dexamethasone or propranolol treatment, but was ameliorated by starvation. Parathyroidectomy produced hypocalcemia in the MStT/W15 tumor rats, confirming the parathyroid dependence of the hypercalcemia. The 7315a tumor produced a milder degree of hypercalcemia, along with elevated serum levels of PRL, ACTH, and corticosterone; serum GH was normal. In high concentrations, PRL and/or GH may stimulate the secretion of PTH as well as enhance dietary calcium absorption, in part through the mediation of 1,25-dihydroxyvitamin D.

Animals↗
PubMed1984

Effect of age and dietary calcium on renal 25(OH)D metabolism, serum 1,25(OH)2D, and PTH.

The purpose of this study was to determine how serum 1,25(OH)2D, renal production of [3H]1,25(OH)2D and [3H]24,25(OH)2D from [3H]25(OH)D, and serum IPTH change with age and dietary Ca restriction. Male Fischer 344 rats aged 3, 13, and 25 mo were placed on either a high-Ca (1.2%) or low-Ca (0.02%) vitamin D-replete diet. After 4 wk, serum was collected, and renal conversion of [3H]25(OH)D3 to [3H]1,25(OH)2D3 and [3H]24,25(OH)2D3 was measured in vitro using isolated renal cortical slices. Serum 1,25(OH)2D and renal [3H]1,25(OH)2D3 production were markedly reduced in 13- and 25-mo-old rats compared with 3-mo-old rats fed the low-Ca diet. In 3-mo-old rats, feeding the low-Ca diet increased serum 1,25(OH)2D by 18-fold and renal [3H]1,25(OH)2D3 production by threefold compared with feeding the high-Ca diet. In 25-mo-old rats, dietary Ca had no effect on these parameters. Renal [3H]24,25(OH)2D3 production was increased in the 13- and 25-mo-old rats compared with the 3-mo-old rats. Serum IPTH increased with age regardless of diet and was significantly increased by the low-Ca diet in 3-mo but not in 13- or 25-mo-old rats. The changes in serum 1,25(OH)2D and renal [3H]1,25(OH)2D3 production observed in this study may account for the previously observed age-related decline in intestinal Ca absorption in this animal model.

25-Hydroxyvitamin D 2↗
PubMed1984

Prolactin stimulation of parathyroid hormone secretion in bovine parathyroid cells.

Previous studies have suggested that prolactin (PRL) may affect calcium (Ca) homeostasis by an action on vitamin D metabolism. In this study, the effects of PRL on parathyroid hormone (PTH) secretion were investigated in dispersed bovine parathyroid cells (PTC). PRL (0.013-1.3 microM) caused concentration-dependent increases in PTH secretion. PRL-stimulated PTH release was apparent as early as 1 h and was progressive thereafter for up to 3 h. PRL enhanced PTH release over a wide range of ambient Ca concentrations (0.5-2.0 microM). Ovine and rat PRL were more effective than bovine PRL in stimulating PTH secretion. This effect was apparently specific for PRL because neither ovine nor bovine growth hormone stimulated PTH secretion. PRL-stimulated PTH release was not mediated through the beta-adrenergic or dopaminergic receptor systems of PTC and was not associated with increased adenosine 3',5'-cyclic monophosphate (cAMP) levels. This study demonstrated a direct effect of PRL to stimulate PTH secretion in vitro. Although these data do not provide evidence for an effect of PRL in vivo, we suggest a mechanism by which PRL may influence parathyroid function and Ca homeostasis in the bovine species.

Adrenergic beta-Agonists↗
PubMed1984

cAMP-dependent reduction in membrane fluxes during relaxation of arterial smooth muscle.

Forskolin, an activator of adenylate cyclase, inhibited contractures induced in rat aorta by norepinephrine (NE) and angiotensin II and by KCl depolarization. The concentration of forskolin required to inhibit NE-induced contractures was significantly lower than required to inhibit KCl-induced contractures (IC50 0.18 +/- 0.01 vs. 2.2 +/- 0.2 microM). Forskolin effectively relaxed NE-induced contractures when active Na+-K+ transport was inhibited. Stimulation of 42K and 36Cl effluxes by NE was inhibited by low concentrations of forskolin. The IC50 for forskolin inhibition of 42K efflux, 0.17 +/- 0.02 M, was similar to that for relaxation of NE contraction. The time course for forskolin-induced increases in adenosine 3',5'-cyclic monophosphate (cAMP) was consistent with that for forskolin-mediated relaxation and its maintenance. Fifty percent inhibition of both NE-induced contractures and NE-stimulated 42K effluxes occurred at levels of cAMP that were 1.4 times basal, and 90% inhibition of both processes was associated with a two to threefold increase in cAMP content. In sharp contrast, the level of tissue cAMP associated with inhibition of KCl contractures was 6-10 times higher than that associated with inhibition of NE-induced contractures. We postulate that cAMP-dependent regulation of membrane fluxes stimulated by receptor occupancy represents a primary mechanism for relaxation of a NE contracture, whereas the processes that regulate depolarization-dependent channels and the phosphorylation of myosin light chain kinase occur at much higher cAMP content and apparently function in a secondary capacity.

Angiotensin II↗
PubMed1984

Maternal-fetal relationships in the parathyroidectomized rat. Intestinal calcium transport, serum calcium, immunoreactive parathyroid hormone and calcitonin.

We studied the role of the parathyroids in the adaptation of intestinal Ca transport that occurs during pregnancy, and whether maternal hypoparathyroidism causes fetal hyperparathyroidism. Serum Ca of pregnant parathyroidectomized (PTX) rats was significantly greater than nonpregnant, PTX animals. Intestinal active Ca transport was increased 2.1- and 2.2-fold by pregnancy in intact and PTX rats, respectively. Serum levels of immunoreactive parathyroid hormone (PTH) were nondetectable in PTX-pregnant rats. Fetuses from PTX rats appeared grossly normal. The serum PTH was not different in fetuses from PTX compared to fetuses from intact mothers and serum Ca, Mg, and P were normal. Thus, alleviation of maternal hypocalcemia during pregnancy in PTX rats may be due to an adaptive increase in intestinal Ca transport, which does not require the parathyroids. Fetuses from PTX mothers were euparathyroid and were protected from Ca deficiency during pregnancy.

Animals↗
PubMed1984

Forskolin increases 1,25-dihydroxyvitamin D3 production by rat renal slices in vitro.

Renal production of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] from 25-hydroxyvitamin D3 (25OHD3) is increased by PTH. The complete mechanism by which PTH modulates renal 25OHD3 metabolism is not known, but there is some evidence that the stimulation of renal cAMP production by PTH may be important. Therefore, we have used forskolin, a direct activator of adenylate cyclase in the intact tissue, to further investigate the role of cAMP in regulating renal 25OHD3 metabolism. The effect of forskolin on renal 25OHD3 metabolism and renal adenylate cyclase activity was measured using isolated renal slices from thyroparathyroidectomized rats previously fed a vitamin D-deficient, low calcium diet. Forskolin added to renal slices in vitro for 4 h increased renal 1,25-(OH)2-D3 production in a concentration-dependent manner. In separate experiments, forskolin was found to increase tissue cAMP in a concentration-dependent manner when added for 5 min. The concentration of forskolin necessary for half-maximal stimulation of adenylate cyclase was 10 microM, and that needed for half-maximal stimulation of 1,25-(OH)2-D3 production was 1 microM. PTH added to renal slices also increased renal 1,25-(OH)2-D3 production, but the effects of PTH and forskolin were not additive. Inclusion of 1,25-(OH)2-D3 in the incubation medium blocked the effect of forskolin on 1,25-(OH)2-D3 production, but it did not block the effect of forskolin on tissue cAMP content. These studies support the concept that forskolin and PTH modulate renal 25OHD3 metabolism though a cAMP-dependent pathway. However, this pathway may be further regulated at sites distal to cAMP production by compounds such as 1,25-(OH)2-D3.

Animals↗
PubMed1984

Effects of hypophysectomy and growth hormone treatment on renal hydroxylation of 25-hydroxycholecalciferol in rats.

Growth hormone stimulates intestinal calcium absorption. This action has been linked to vitamin D metabolism. We have investigated the effects of hypophysectomy and GH treatment on renal metabolism of 25-hydroxycholecalciferol (25-OH-D3). Renal hydroxylation of 25-OH-D3 was measured in vitro using the renal slice technique. Experiments were performed in young F344 rats fed a vitamin D-replete, low calcium diet for 4 weeks. In hypophysectomized rats, renal conversion of 25-OH-D3 to 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) was markedly reduced compared with sham-operated rats. Renal conversion of 25-OH-D3 to 24,25-(OH)2D3 was markedly increased in hypophysectomized rats compared with sham-operated rats. Treatment of hypophysectomized rats with rat GH (rGH) for 10 days resulted in a significant increase in renal conversion of 25-OH-D3 to 1,25-(OH)2D3 and a significant decrease in conversion to 24,25-(OH)2D3. Rat GH treatment caused no significant changes in serum levels of immunoreactive parathyroid hormone. Serum calcium concentrations were similar in all groups, and serum phosphorus was low in hypophysectomized rats. Treatment of hypophysectomized rats with ovine GH for 6 days caused changes which were much less pronounced than those induced by rGH. Renal conversion of 25-OH-D3 to 1,25-(OH)2D3 and 24,25-(OH)2D3 correlated well with growth rate (weight gain). These results suggest that GH, either directly or indirectly, modulates renal metabolism of 25-OH-D3.

24,25-Dihydroxyvitamin D 3↗
PubMed1983

Activation of renal adenylate cyclase by forskolin: assessment of enzymatic activity in animal models of the secondary hyperparathyroid state.

The effects of forskolin on kidney slice cyclic AMP content and membrane adenylate cyclase activity were studied in order to determine whether or not activation of the enzyme by forskolin was affected in experimental animal models of the secondary hyperparathyroid state. Forskolin was found to be a potent activator of renal adenylate cyclase in rats and chicks, and the diterpene produced a marked potentiation of the cyclic AMP response to parathyroid hormone (PTH). The diterpene had no effect on the binding of PTH to renal receptors. Activity of adenylate cyclase in the presence of forskolin was similar in renal membranes from either vitamin D-deficient rats or chicks compared to control. Forskolin did not restore full responsiveness to PTH in renal slices from chicks raised on diets that were deficient in either vitamin D or calcium although the diterpene was capable of potentiating the cyclic AMP response to PTH in these tissues. Forskolin also augmented the activation of membrane adenylate cyclase by PTH although this effect of the diterpene was much less prominent in membrane preparations than that observed in renal slices. This study provided additional evidence that the downregulation of renal PTH-dependent adenylate cyclase in experimental models of secondary hyperparathyroidism is due to a specific reduction in receptor-mediated regulation of cyclic AMP formation. Adenylate cyclase activity as assessed by forskolin-stimulated enzyme activity was fully maintained in kidney membranes from these animal models. Thus, forskolin appears to be a useful drug for measuring total enzymatic activity in situations where altered responsiveness of adenylate cyclase to hormones has been demonstrated to be mediated by changes in hormone receptors.

Adenylyl Cyclases↗
PubMed1983

Forskolin does not activate sperm adenylate cyclase.

Forskolin, a potent activator of adenylate cyclase, has been proposed to activate this enzyme by a direct interaction with the catalytic subunit. To test this hypothesis, we examined the effects of forskolin on sperm cyclic AMP content and sperm adenylate cyclase activity. Forskolin or cholera toxin did not increase cyclic AMP content in either bull or boar sperm, whereas the inhibitors of phosphodiesterase, caffeine and methylisobutylxanthine, significantly increased sperm cyclic AMP content. Forskolin, NaF, and guanylimidodiphosphate did not activate the adenylate cyclase of either sperm membranes or cytosol. When homogenates of rat, guinea pig, or bull testes were centrifuged at 100,000 X g, the supernatant was found to contain a forskolin-stimulated adenylate cyclase. Further centrifugation of this 100,000 X g supernatant fraction at 250,000 X g for 3 hr quantitatively sedimented the forskolin-sensitive enzyme activity. We conclude that forskolin does not activate either the cytosolic or membrane-bound adenylate cyclase of mammalian sperm.

Adenylyl Cyclases↗
PubMed1982

Alpha-2 adrenergic activation inhibits forskolin-stimulated adenylate cyclase activity and lipolysis in human adipocytes.

Forskolin at 10 muM caused a 100-fold increase in the intracellular concentration of cyclic AMP and a 6-fold increase in glycerol release in the human adipocyte. These responses are comparable to those prompted by 10 muM isoproterenol. The effects of forskolin on cyclic AMP and lipolysis were dose-dependent. Alpha-2 adrenergic activation, achieved with 10 muM epinephrine and 30 muM propranolol, significantly inhibited forskolin-stimulated cyclic AMP accumulation and glycerol release, shifting the dose-response curves to the right. Forskolin at 10 muM caused a 4.5-fold increase in the adenylate cyclase activity of human adipocyte membranes. When either isoproterenol or epinephrine (0.1 mM) was combined with forskolin, the magnitude of response was substantially greater than the sum of responses achieved by each agent incubated alone.

Adenylyl Cyclases↗
PubMed1982

Maintenance of normocalcemia by continuous infusion of the synthetic bovine parathyroid hormone (1-34) in parathyroidectomized rats.

This work was conducted to estimate the replacement dose of the synthetic bovine parathyroid hormone [PTH(1-34)] that is required for maintenance of serum calcium (Ca) in parathyroidectomized (PTX) rats. Male rats were PTX and used in this study only if serum Ca was reduced to at least 7 mg/dl. We found that a solution of 2% cysteine, 150 mM NaCl, and 1 mM HCL was superior to 20 mM acetic acid for maintenance of biological activity of PTH (1-34) in situ during the period of hormone infusion studied. The PTH dose-calcemic response relationship was investigated using PTH in doses of 0.6, 1, and 3 U/h. The infusion of 1 U PTH per hour raised Ca to the normal level, whereas rats infused with 0.6 U/h were hypocalcemic and 3 U/h resulted in marked hypercalcemia. To extend this observation we carried out an infusion of 1 U PTH per hour for 14 days. We found that this infusion rate of bovine PTH (1-34) provided a relatively stable level of serum calcium with modest fluctuation from normocalcemic to somewhat hypercalcemic levels for the entire 14-day period of PTH infusion. Serum calcitonin was also elevated during the infusion period and then returned to the initial level when PTH treatment was stopped. After the minipumps containing PTH were removed, the serum Ca dropped rapidly to 5 mg/dl, which was significantly lower than the control (vehicle-infused) or initial values of serum Ca (7 mg/dl). Infusion of PTH at 3 U/h for 4 days did not produce this rebound hypocalcemia after the pumps were removed. Serum Ca in those experiments returned to the initial level after hormone treatment was discontinued.

Animals↗
PubMed1982

Renal parathyroid hormone receptors in the chick: downregulation in secondary hyperparathyroid animal models.

We characterized the binding of 125I-[Nle8, Nle18, Tyr34]parathyroid hormone-(1-34) amide [125I-nlPTH-(1-34)] to renal plasma membranes prepared from chicks to determine the effects of secondary hyperparathyroid states on renal PTH receptors. This radioligand exhibited specific binding to membranes with high affinity (Kd, 2-3 X 10(-9) M). Agonists or competitive antagonists of PTH were effective in competing for binding sites labeled with 125I-nlPTH-(1-34), whereas an inactive fragment of PTH, salmon calcitonin, and bovine growth hormone did not compete with the radioligand for renal PTH receptors. Newly hatched chicks raised on control diet with adequate vitamin D and calcium or diets deficient in either vitamin D or calcium were used to study the regulation of renal PTH receptors in experimental models of secondary hyperparathyroidism. We found that both experimental diets resulted in marked hypocalcemia and progressive loss of renal cyclic AMP responsiveness to PTH in vitro. Associated with this refractoriness to the hormone was a marked reduction in PTH receptors in membranes from both vitamin D-deficient and calcium-deficient chick kidney. No change in the affinity of the PTH receptors was found. Vitamin D3, in a single dose of 250 micrograms, partially restored serum calcium of vitamin D-deficient birds toward normal by 72 h and also partly restored renal cyclic AMP responsiveness to PTH and the PTH receptor number toward control values. We conclude that renal refractoriness to PTH observed in experimentally hyperparathyroid animals models is due to a marked loss of plasma membrane receptor sites for PTH without an apparent change in the affinity of the receptors for the hormone.

Adenylyl Cyclases↗
PubMed1982

Serum calcium and parathyroid hormone during the reproductive cycle in normal and vitamin D-deficient rats.

This study was designed to investigate the ability of the vitamin D-deficient (-D) rat to maintain calcium (Ca) homeostasis during pregnancy. Serum Ca and immunoreactive parathyroid hormone (iPTH) were measured before and during pregnancy and after lactation in normal (+D) and -D rats. Serum Ca increased from 9.4 +/- 0.3 to 10.2 +/- 0.2 mg/dl during the first 3 days of pregnancy in +D animals and then declined throughout the remainder of gestation to 9.7 mg/dl at 17 days of gestation. In contrast, serum Ca rose progressively during the first 17 days of pregnancy in -D rats from 5.5 +/- 0.2 to 6.7 +/- 0.4 mg/dl. As expected, the -D rats had markedly elevated serum iPTH, but there were no changes in circulating iPTH during pregnancy in either animal model, even though serum Ca increased significantly during pregnancy in -D animals and Ca decreased in the +D rats. After lactation, serum Ca of -D rats increased 2 mg/dl before returning to prepregnancy levels. These results suggest that there are physiological mechanisms which appear to be independent of vitamin D and are responsible for elevating serum Ca during pregnancy and lactation.

Animals↗