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I thought this recent study would be really interesting for most people here. [mention]gbolduev[/mention] you will absolutely find this interesting.
http://www.fasebj.org/content/31/1_Supplement/856.11.short
"Adaptation to potassium depletion in human : role of progesterone ?"
Abstract
In this study, we examined whether reduction in the intake of K+ induce lasting changes in the plasma concentration of circulating steroids. We have previously shown that plasma progesterone (PG) levels specifically increases in response to chronic and sustained K+ depletion in male and female mice. In this physiological context, progesterone regulates renal K+ handling by stimulating the expression of H,K-ATPase type 2 (HKA2) through a RU486 (PG receptor antagonist)-sensitive pathway. The human adrenal steroidogenesis strongly differs from rodents because of the presence of a CYP17 activity that metabolizes PG into 17-OH PG and may prevent its accumulation and release in the plasma. To address the role of PG in renal adaptation to K depletion in human, we designed a cross-over protocol in which healthy subjects were submitted to a 7-days K+ depleted diet in the absence (placebo period) or presence of a PG antagonist (RU486 period). We studied their renal adaptation to K+ depletion and the induced changes in plasma adrenal steroids concentrations before and 1h after stimulation by ACTH (SYNACTHENE®). Since this adaptation could be relevant in the case of severe and chronic renal hypokalemia, plasma adrenal steroids were measured in patients with chronic severe renal hypokalemia related to a congenital salt losing tubulopathy, the Gitelman syndrome.
During the two periods, a week of reduction of dietary K+ intake induced both daily urinary excretion of K+ and fractional excretion of K+ decreased by a factor 2, without affecting daily urinary excretion or fractional excretion of Na+. Under placebo condition, plasma K+ concentration decreased by 0.3 ± 0.1 mmol/l (p= 0.0180) and subjects became slightly hypokalemic, without change in plasma concentrations of sodium, chloride, bicarbonate or creatinine. As expected, plasma aldosterone decreased by 55% and more surprisingly, DHEA decreased by 20% but the other steroids concentration (Cortisol, PG, 17-OH PG, deoxycorticosterone, delat4-androstenedione) are not modified neither under basal or after SYNACTHENE® treatment. Under RU486 treatment, the decrease of the plasma K+ level is much faster than under placebo and the plasma aldosterone concentration is decreased even more than under the placebo period indicating that RU486 interferes with the regulation of the K+ balance. The basal level of steroids is similar in Gitelman patients compared to healthy volunteers. However, the stimulation of adrenal steroidogenesis by SYNACTHENE® induces a stronger rise of PG, 17-OH PG and delta4-androstenedione indicating that in Gitelman patients the 3bHSD activity is stimulated but not activated.
Altogether, these results indicate that, in men, a moderate reduction of the K+ intake does not result in a visible rise of plasma PG but the effect of RU486 and the putative stimulation of the adrenal 3bHSD-dependent steps in Gitelman patients may indicate that this hormonal system may be relevant in the regulation of K+ balance.
http://www.fasebj.org/content/31/1_Supplement/856.11.short
"Adaptation to potassium depletion in human : role of progesterone ?"
Abstract
In this study, we examined whether reduction in the intake of K+ induce lasting changes in the plasma concentration of circulating steroids. We have previously shown that plasma progesterone (PG) levels specifically increases in response to chronic and sustained K+ depletion in male and female mice. In this physiological context, progesterone regulates renal K+ handling by stimulating the expression of H,K-ATPase type 2 (HKA2) through a RU486 (PG receptor antagonist)-sensitive pathway. The human adrenal steroidogenesis strongly differs from rodents because of the presence of a CYP17 activity that metabolizes PG into 17-OH PG and may prevent its accumulation and release in the plasma. To address the role of PG in renal adaptation to K depletion in human, we designed a cross-over protocol in which healthy subjects were submitted to a 7-days K+ depleted diet in the absence (placebo period) or presence of a PG antagonist (RU486 period). We studied their renal adaptation to K+ depletion and the induced changes in plasma adrenal steroids concentrations before and 1h after stimulation by ACTH (SYNACTHENE®). Since this adaptation could be relevant in the case of severe and chronic renal hypokalemia, plasma adrenal steroids were measured in patients with chronic severe renal hypokalemia related to a congenital salt losing tubulopathy, the Gitelman syndrome.
During the two periods, a week of reduction of dietary K+ intake induced both daily urinary excretion of K+ and fractional excretion of K+ decreased by a factor 2, without affecting daily urinary excretion or fractional excretion of Na+. Under placebo condition, plasma K+ concentration decreased by 0.3 ± 0.1 mmol/l (p= 0.0180) and subjects became slightly hypokalemic, without change in plasma concentrations of sodium, chloride, bicarbonate or creatinine. As expected, plasma aldosterone decreased by 55% and more surprisingly, DHEA decreased by 20% but the other steroids concentration (Cortisol, PG, 17-OH PG, deoxycorticosterone, delat4-androstenedione) are not modified neither under basal or after SYNACTHENE® treatment. Under RU486 treatment, the decrease of the plasma K+ level is much faster than under placebo and the plasma aldosterone concentration is decreased even more than under the placebo period indicating that RU486 interferes with the regulation of the K+ balance. The basal level of steroids is similar in Gitelman patients compared to healthy volunteers. However, the stimulation of adrenal steroidogenesis by SYNACTHENE® induces a stronger rise of PG, 17-OH PG and delta4-androstenedione indicating that in Gitelman patients the 3bHSD activity is stimulated but not activated.
Altogether, these results indicate that, in men, a moderate reduction of the K+ intake does not result in a visible rise of plasma PG but the effect of RU486 and the putative stimulation of the adrenal 3bHSD-dependent steps in Gitelman patients may indicate that this hormonal system may be relevant in the regulation of K+ balance.
