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.

Angiotensin II Type 2 Receptor Inhibits Prorenin Processing in Juxtaglomerular Cells

“…JG cells had a 48-h rest period before the beginning of the experiments. Immunofluorescence staining for renin confirmed that 87 4% of the cells (n 5 primary cultures) were positive for renin at 60 h after isolation (11)(12)(13)(14).…”

“…In accordance with the guidelines and practices established by the Keio University Animal Care and Use Committee, JG cells were isolated from kidneys of male Sprague-Dawley rats (100-150 g) as previously described (11)(12)(13)(14). JG cells were suspended at 10 6 cells/ml in culture medium consisting of RPMI 1640 with 25 mmol/l N-2-hydroxyethylpiperazine-N -2-ethane sulfonic acid, 0.3 g/l L-glutamine, 100 µg/ml streptomycin, 100 U/ml penicillin, 0.66 U/l insulin, and 10% fetal bovine serum.…”

“…Renin activity was determined as previously described (12). Samples were incubated for 1 h at 37 ºC with plasma from bilaterally nephrectomized male Sprague-Dawley rats as the renin substrate, and renin activity was determined by the generation of Ang I from a plasma angiotensinogen substrate.…”

The Thyroid and the Kidney: A Complex Interplay in Health and Disease

“…Interestingly, administration of ACE-inhibitors in hyperthyroid animals with hypertension led to a decrease in BP to normal levels with increased heart rate and CO, indicating that in hyperthyroidism the predominant factor of hypertension is the RAS system and not the increased CO (31). Data from in vitro studies reported that administration of thyroid hormones increases the synthesis and secretion of renin by the rat juxtaglomerular cells (74). Notably, there are no data regarding the synthesis or/and secretion of pro-renin and thyroid hormones.…”

The renin–angiotensin system in thyroid disorders and its role in cardiovascular and renal manifestations

“…Ichihara et al (1998) found that triiodothyronine (T 3 ) administration increases renin secretion, renin content, and renin mRNA in rat juxtaglomerular cell cultures. Various authors observed this direct action in cardiac tissue from hyperthyroid rats and reported that thyroid hormones directly stimulate renin mRNA and the promoter activity of the human renin gene via thyroid hormone regulating elementdependent mechanisms (Gilbert et al 1994, Kobori et al 1997a,b, 2001).…”