Differential effects of thyroid hormone on renin secretion, content, and mRNA in juxtaglomerular cells

Abstract

The effects of thyroid hormone on renin secretion, renin content, and renin mRNA levels in juxtaglomerular (JG) cells harvested from rat kidneys were determined by radioimmunoassays and reverse transcriptase-polymerase chain reaction. Despite a lack of immediate effect, incubation with triiodothyronine dose dependently increased renin secretion during the first 6 h and elevated renin content and renin mRNA levels during the subsequent period. Simultaneous incubation with triiodothyronine and the calcium ionophore A-23187 abolished the increase in renin secretion and attenuated the increase in renin content but did not affect the increase in renin mRNA levels. During simultaneous incubation with triiodothyronine and the adenylate cyclase inhibitor SQ-22536 or membrane-soluble guanosine 3',5'-cyclic monophosphate (cGMP), the increases in renin secretion, content, and mRNA were similar to those observed in the presence of triiodothyronine alone, except for a cGMP-induced attenuation of the increase in renin secretion. These findings suggest that thyroid hormone stimulates renin secretion by JG cells through the calcium-dependent mechanism, whereas the stimulation of renin gene expression by thyroid hormone does not involve intracellular calcium or cyclic nucleotides.

Fig. 1

Renin immunofluorescence in a representative primary culture of juxtaglomerular (JG) cells incubated for 72 h after isolation; magnification, ×400.

Fig. 2

Effects of 0 (○), 1 (•), 10 (□), 100 (■), and 1,000 pM (△) triiodothyronine on renin secretion rate (RSR) of primary cultures of JG cells prepared from rat kidneys. ANG I, angiotensin I. Each value was calculated from data obtained in 5 primary cultures. *P < 0.05 vs. 0 h value. †P < 0.05 vs. 0 pM value.

Fig. 3

Effects of 0 (○), 1 (•), 10 (□), 100 (■), and 1,000 pM (△) triiodothyronine on renin content of primary cultures of JG cells harvested from rat kidneys. Each value was calculated from data obtained in 5 primary cultures. * P < 0.05 vs. 0 h value. †P < 0.05 vs. 0 pM value.

Fig. 4

A: representative electrophoretogram showing incubation period-dependent effect of 100 pM triiodothyronine on renin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels of JG cells; bp, base pair. B: representative electrophoretogram showing concentration-dependent effect of 24-h incubation with triiodothyronine on renin and GAPDH mRNA levels of JG cells. C: effects of 0 (○),1(•), 10 (□), 100 (■), and 1,000 pM (△) triiodothyronine on renin mRNA level (ratio of GAPDH mRNA level, %) in primary cultures of JG cells harvested from rat kidneys. Each value was calculated from data obtained in 5 cultures. * P < 0.05 vs. 0 h value. †P < 0.05 vs. 0 pM value.

Fig. 5

Representative electrophoretogram showing effect of A-23187, SQ-22536, and DBcGMP on renin and GAPDH mRNA levels in JG cells incubated in absence and presence of 100 pM triiodothyronine for 24 h.