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The new edition of Werner's The Thyroid is so massive a monograph that anyone might be forgiven for supposing that all must now be light as regards the thyroid and its hormones. Such a conclusion would be much in error: many important areas remain most murky. Some of the problems involved in understanding the metabolism of thyroid hormones at the cellular level received a recent airing in the lecture of Professor Reed Larsen at the 1987 meeting of the British Endocrine Societies (Larsen, 1987). Although it is now generally accepted that the important thyroid hormone for the cells is tri-iodothyronine (T3), it is not clear precisely how the supply is matched to the cellular need, for T3 forms only a small proportion of the thyroid secretion, the predominant hormone secreted being thyroxine (T4). The cellular supply of T3 depends largely on conversion of T4 to T3 by an enzyme
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SUMMARY
The excretion of sodium, potassium and water, and the changes of glomerular filtration rate (g.f.r.) in response to intravenous infusions of hypertonic saline have been studied in normal and adrenalectomized rats.
The increase in sodium excretion in response to infusion was considerably depressed after adrenalectomy. It was not restored to normal by cortisone or cortisol administration, although the adrenalectomized rats treated with these steroids were able to excrete water after a water load as rapidly as normal rats.
Potassium excretion was increased to a similar extent by the infusions in both normal and adrenalectomized rats.
g.f.r. rose in both groups during the infusion but the rise was depressed by adrenalectomy. In both normal and adrenalectomized rats treated with cortisone, g.f.r. remained elevated throughout the infusion, but the initial rise was less rapid in the latter than in the normal animals. In adrenalectomized rats maintained on 1% saline only, the rise of g.f.r. was not sustained and by the 4th hr of infusion had fallen to the pre-infusion level. When i.v. cortisol was given immediately before the infusion, the initial rise of g.f.r. was restored to normal.
Comparison of the changes of g.f.r. with those of sodium excretion suggested that impairment of sodium excretion during the infusions was due, in part at least, to a change in renal tubular reabsorption of sodium following adrenalectomy.
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ABSTRACT
The influence of adrenalectomy and administration of aldosterone on potassium secretion by colonic epithelium was studied in vivo in rats, particularly in relation to potassium adaptation (induced by feeding a potassium-rich diet) and the response to acute i.v. administration of a potassium load. Adrenalectomy (rats maintained on dexamethasone and saline) impaired the development of potassium adaptation or considerably reduced it if the rats had been previously adapted. The partial adaptation observed in the adrenalectomized rats may be related to the increased plasma potassium concentration developed when these rats received the potassium-rich diet.
Within 2 h of acute aldosterone administration, the response of the potassium secretion rate to acute potassium loading in adrenalectomized rats was significantly improved. When aldosterone (2 μg/day per 100 g body weight, given by osmotic minipump) was added to the replacement treatment, the plasma concentration of potassium was similar to that of the intact rats, and both potassium adaptation and the response to the acute potassium load were completely restored. Transepithelial potential difference and sodium transport were not stimulated, being similar to the values in intact rats. Considerable changes in potassium secretion induced by acute potassium loading did not significantly affect sodium transport.
The findings suggest that the sodium and potassium epithelial pathways are, to a large extent, independently influenced by aldosterone. Aldosterone appears to be essential for complete adaptation and, in a relatively low dose, can completely restore potassium adaptation and the response to acute potassium loads in adrenalectomized rats.
J. Endocr. (1988) 117, 379–386
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ABSTRACT
The effect of hypothyroidism on potassium adaptation (shown by increased potassium secretion in response to potassium loading) and on the action of aldosterone on potassium secretion and sodium fluxes was examined in the rat distal colon.
Potassium adaptation, particularly the response to an acute potassium load, was impaired by hypothyroidism which also considerably reduced the rise of transepithelial electrical potential difference (p.d.) of total and transcellular (active) lumen-to-plasma sodium fluxes and of potassium secretion normally produced by aldosterone. These changes were, in part, corrected by a short period (3 days) of tri-iodothyronine replacement. Moreover in aldosterone-treated hypothyroid rats, amiloride in the lumen was considerably less effective in reducing the p.d. and sodium fluxes than in aldosterone-treated normal rats.
The intracellular sodium transport pool was greater in the hypothyroid than in the normal rats (5·0± 1·1 (s.e.m.) nmol/mg dry weight compared with 2·9 ± 0·2 nmol/mg dry weight; P<0·02). Aldosterone increased the pool in the normal but not in the hypothyroid rats while amiloride had little effect on the pool in the aldosterone-treated hypothyroid rats but almost abolished it in aldosterone-treated normal rats.
Aldosterone plays a major part in the adaptation of colonic sodium and potassium transport to sodium depletion or potassium excess; these adaptations were much impaired in hypothyroid animals. The present results are consistent with a deficiency in aldosterone induction of potassium- and amiloride-sensitive sodium pathways in the apical membrane of colonic epithelial cells in hypothyroid rats, a deficiency which limits the stimulant effect of aldosterone on sodium and potassium transport.
Journal of Endocrinology (1990) 124, 47–52
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SUMMARY
The effect of adrenalectomy on the increase of the transmucosal potential difference (p.d.) of the colon of the rat induced by Na depletion, together with the action of aldosterone on the p.d. and on colonic Na+ and Cl− transport, and K+ and bicarbonate secretion have been investigated. Adrenalectomy increased the Na+ content in the stool, an effect reversed by treatment with aldosterone. When Na+-depleted rats were adrenalectomized and maintained on cortisone, the elevated p.d. fell to levels below those found in normal rats. Aldosterone given intravenously (i.v.) in physiological doses increased the p.d. in normal, adrenalectomized and Na+-depleted adrenalectomized rats after a latency period of 80–110 min., and the p.d. tended to rise further when injections were continued for several days. The p.d. gradient along the colon after treatment with aldosterone was similar to that of Na+-depleted rats, the highest p.d. being at the distal end of the descending colon. Cortisol intravenously increased the p.d. but the effect was small in comparison with that of aldosterone.
Measurement of ionic fluxes in the descending colon of adrenalectomized rats showed that treatment with aldosterone produced an increase in Na+ and water absorption, and in K+ secretion, but had no effect on bicarbonate secretion. The effects of aldosterone on the transmucosal p.d. and ion transport were similar to those of Na+ depletion.
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SUMMARY
The effect of aldosterone on the colonic transmucosal potential difference (p.d.) was examined in normal, adrenalectomized and Na+ depleted rats. Continuous intravenous infusion of aldosterone in conscious animals was more effective than single i.v. injection and over the dose range 0·5–50 μg./hr. for 6 hr., p.d. increased linearly with log dose and returned to the pre-infusion levels 16–24 hr. after stopping infusion. Only a region 2–4 cm. from the anus responded to low doses, but with high doses an increasing length of colon responded. Cortisone (250 μg. daily) intramuscularly maintained adrenalectomized rats even when severely Na+ depleted without affecting the p.d. Cortisone (2·5 mg. daily, i.m.) raised the p.d. but the effect of low doses of aldosterone was unchanged. Neither Na+ depletion nor pentobarbitone anaesthesia affected the action of aldosterone but large doses of spironolactone reduced it. Aldosterone was effective when applied locally by submucosal injection in very low dose but was almost ineffective even in very large dose in the lumen. Again the most sensitive region was 2–4 cm. from the anus. Ouabain (10-3 m) injected into the submucosa rapidly reduced the increased p.d. but was ineffective in the lumen.
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ABSTRACT
The cellular sodium transport pool and sodium transepithelial fluxes were investigated in vivo in rat distal colon in relation to sodium loading by intravenous infusion (3·5 h), and to short (4 h) and prolonged (72 h) i.v. administration of aldosterone. Considerable natriuresis and increase in body sodium content were produced by the sodium load but there was no significant effect on the transcellular sodium flux (active absorption from lumen to plasma) or on the sodium transport pool. Both short and prolonged aldosteronism produced similar increases in the transport pool and in the transcellular sodium flux, but the transepithelial electrical potential difference (p.d.) was significantly greater in rats given the prolonged infusion. Addition of amiloride to the solution in the lumen of the colon almost completely abolished the p.d., the transport pool and the transcellular sodium flux of the rats receiving prolonged infusion, but had much less effect in those given the short infusion. The time-course of recovery of p.d. following prolonged aldosteronism was similar to that described for the turnover rate of rat colonic epithelial cells.
Lithium within the lumen had no significant effect in untreated rats but after prolonged aldosterone infusion lithium reduced the p.d. and the transcellular sodium flux although the transport pool was not reduced. These findings are consistent with the hypothesis that aldosteronism renders the apical membranes of the epithelial cells permeable to lithium and that intracellular accumulation of lithium depresses active sodium transfer.
The observations are interpreted in terms of an epithelial model in which aldosterone induces amiloride-sensitive pathways (diffusion channels permeable to sodium and lithium) in the apical membrane which totally replace the amiloride-insensitive pathways when aldosteronism is prolonged; the resulting expansion of the sodium transport pool is the stimulus for increased active sodium transport across the basolateral membranes.
J. Endocr. (1987) 112, 247–252
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SUMMARY
Transmucosal electrical potential difference and short-circuit current of an in-vitro preparation of mucosal epithelium of rat colon were almost abolished and active sodium transport ceased when ouabain (1 mmol/l) was present on the serosal side of the epithelium.
A considerable fraction of the total ATPase activity in the mucosa was sodium dependent and concentrations of ouabain of 0·5 mmol/l or more completely eliminated the activity of this fraction.
Adenosine triphosphatase activities in mucosa taken from normal, hypothyroid, aldosterone-treated and sodium-depleted rats were compared. The activity of the ouabain-sensitive, sodium-dependent fraction was similar in all groups except for the hypothyroid rats in which it was considerably reduced.
There was no evidence from the present study that the increased active sodium transport by colonic mucosa, associated with aldosterone action or sodium depletion, depended upon a change in ATPase activity. In hypothyroidism, reduction of ouabain-sensitive ATPase activity may be responsible for the observed impairment of the sodium transport mechanism.
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SUMMARY
Rats were given a continuous intravenous infusion of aldosterone for up to 16 days. The rate of urinary Na+ excretion was initially depressed, but 'escape' occurred in about 4 days. Diurnal variation of Na+ excretion rate persisted even when the Na+ intake rate was controlled by infusion and when there was a continuous high level of exogenous aldosterone. After stopping aldosterone infusion, a transient rise in the rate of Na+ excretion was observed. Colonic transepithelial potential difference remained elevated as long as the infusion was continued and the short-circuit current, which is largely accounted for by active Na+ absorption, was increased. Stool Na+ content was reduced. The Na+ transport system of colonic epithelium, unlike that of kidney, does not appear to escape from the effect of aldosterone.
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SUMMARY
The effect of aldosterone on the ionic composition of colonic epithelial cells and on lithium absorption rate was studied by experiments on rats in vivo. Aldosterone considerably increased the rate of sodium absorption without measurably altering the sodium and potassium content of the epithelium. Aldosterone did not alter the electrical resistance of the tissue. With lithium in the lumen, the net sodium fluxes in the colon were similar in normal and aldosterone-stimulated rats but the rate of diffusion of lithium across the epithelium was greater in the aldosterone-stimulated group. The amount of lithium accumulating in the epithelial layer was also considerably increased by aldosterone stimulation. Aldosterone appears to increase the permeability of the mucosal (luminal) barrier allowing increased entry of lithium into the colonic epithelial cells.
