In vitro 1,25-dihydroxycholecalciferol (1,25(0H)2D3) decreased levels of preproparathyroid(preproPTH) hormone mRNA. We have now pursued these studies in vivo in the rat. Rats were administered vitamin D metabolites i.p. and the levels of preproPTH mRNA were determined in excised parathyroidthyroid glands by blot hybridization. PreproPTH mRNA levels were <4% of basal at 48 h after 100 pmol 1,25(OH)2D3, with no increase in serum calcium. Gel blots showed that 1,25(OH)2D3 decreased preproPTH mRNA levels without any change in its size (833 basepair). Microdissected parathyroids after 1,25(0H)2D3 (100 pmol) showed mRNA levels for preproPTH were 40±8% of controls, but for f-actin were 100% of controls.The relative potencies of vitamin D metabolites were: 1,25(0H)2D3> 24,25(0H1)D3> 25(OH)D3 > vitamin D3. In vitro nuclear transcription showed that 1,25(0H)2D3-treated (100 pmol) rats' PTH transcription was 10% of control, while j5-actin was 100%. These results show that 1,25(0H1)D3 regulates PTH gene transcription. PTH stimulates 1,25(OH)2D3 synthesis, which then inhibits PTH synthesis, thus completing an endocrinological feedback loop.

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This study explores the role of K+ and aldosterone in the regulation of mRNA of the ATP-sensitive, inwardly rectifying K+ channel, ROMK, in the rat kidney. K+ deficiency downregulated ROMK mRNA in cortex to 47.1 ± 5.1% of control ( P < 0.001) and in medulla to 56.1 ± 3.4% ( P < 0.001). High-K+ diet slightly increased ROMK mRNA in medulla to 122 ± 9% ( P < 0.05 vs. control). Adrenalectomy (Adx) downregulated cortical ROMK mRNA to 30.7 ± 6.8% ( P < 0.001 vs. control), and increased it in medulla to 138 ± 12.9% ( P < 0.02 vs. control). In Adx rats, K+ deficiency decreased ROMK mRNA in cortex and medulla similar to intact rats. The α1- and β1-Na-K-ATPase subunits were regulated in parallel to that of ROMK. In medulla, ROMK mRNA correlated with serum K+ concentration at R = 0.9406 ( n = 6, P < 0.001) and α1-Na-K-ATPase mRNA at R = 0.9756 ( n = 6, P < 0.001). ROMK2 also correlated with serum K+ concentration ( R = 0.895; n = 6, P < 0.01). These results show that cortical ROMK expression is regulated by aldosterone and K+, whereas the medullary ROMK mRNA is regulated by serum K+.

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This study was undertaken to evaluate the effect of long-term diabetes on Na(+)-K(+)-ATPase in isolated nephron segments in five groups of rats: 1) controls of 7 wk duration (7 WD), 2) diabetes mellitus (DM) of 7 WD, 3) DM of 7 WD treated with insulin replacement, 4) DM rats of 25 WD, and 5) control rats of 25 WD. The blood glucose (BG) values in the first three groups were 123 +/- 9, 450 +/- 25, and 302 +/- 30 mg/dl; the glomerular filtration rate (GFR) was 1.34 +/- 0.08, 1.80 +/- 0.10, and 1.77 +/- 0.08 ml/min; and urinary sodium excretion was 0.94 +/- 0.05, 1.76 +/- 0.10, and 1.40 +/- 0.07 mu eq/min. Na(+)-K(+)-ATPase in group 2 increased in all segments studied (P < 0.001, group 1 vs. 2 for all). In group 3, Na(+)-K(+)-ATPase normalized in proximal convoluted (PC), proximal straight (PS), and distal convoluted (DC) tubules (P < 0.001, group 2 vs. group 3 for all), whereas in the outer medullary thick ascending limb (OMTAL) the correction was partial and in the CTAL and CCD there was no correction. In group 4 BG was 420 +/- 20 mg/100 ml compared with 123 +/- 9 in group 5 (P < 0.001), and GFR was 1.19 +/- 0.11 ml/min vs. 1.15 +/- 0.11 in group 5 (P = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)