Antidiuretic Action of Prolactin in the Rat with Diabetes Insipidus

Abstract

Rats with hereditary hypothalamic diabetes insipidus, devoid of endogenous ADH, exhibited a prompt antidiuresis when injected subcutaneously or intraarterially with ovine prolactin. The antidiuresis was accompanied by a decrease in free water clearance and an increase in urine osmolality without a change in osmolal clearance or creatinine excretion. Measurement of PAH and inulin clearances indicated that prolactin had no effect on renal plasma flow or glomerular filtration rate. Prolactin injection caused a transient decrease in urinary sodium excretion, but proximal tubular sodium reabsorption, estimated by lissamine green transit time, was unaffected. The antidiuretic effect of prolactin could not be attributed to ADH contamination of the ovine prolactin preparation. Kidney cyclic AMP content was increased significantly 5 min after injection of prolactin. Thus, prolactin has an antidiuretic effect similar to that which occurs as a result of ADH action on the kidney and does not require either the release or the presence of ADH in order to cause the antidiuresis. Further, the impaired water excretion cannot be attributed to an increase in proximal tubular sodium reabsorption or to alteration of renal hemodynamics. It is suggested that prolactin has a direct ADH-like action on the kidney resulting in antidiuresis.

Prolactin Release in Response to Infusion of Isotonic or Hypertonic Saline

“…Infusion or injection of prolactin can diminish the renal response to a saline or water load in mammals (Lockett & Nail, 1965;Horrobin et al 1971;Lucci et al 1975), and this effect is not due to vasopressin contamination of the prolactin preparation nor does it require the presence of endogenous vasopressin (Miller & Van Gemert, 1976).…”

“…Prolactin has been shown to be capable of affecting the renal response to oral water loading (Lockett & Nail, 1965;Horrobin, Lloyd, Lipton, Burstyn, Durkin & Muiruri, 1971) and saline infusion (Lucci, Bengele & Solomon, 1975;Miller & Van Gemert, 1976). In order to establish a direct role for prolactin in volume or osmoregulation it is necessary to show that either extracellular fluid volume or plasma osmolality (or both) can influence pituitary prolactin release.…”

Peptide hormones and the regulation of sodium excretion.

“…126 Functional consequences of prolactin administration have been clouded by pharmacological doses of impure preparations. Effects of the peptide to increase renal hemodynamics, 127 ' m impair volume expansion natriuresis, 129 and act as an antidiuretic agent 130 have been reported in some animal studies but not observed in humans. 126 ' m It would seem that the renal actions, if any, of prolactin are minor at best.…”

“…The mechanism of action of insulin does not appear to involve the classic second messengers discussed earlier. 130 Since the kidneys account for the degradation of a considerable fraction of circulating insulin, 130 ' m binding and uptake could represent catabolism of the peptide rather than initiation of a hormone-stimulated effect on the cell. These comments notwithstanding, it seems clear that insulin decreases urinary sodium excretion acutely.…”

Effect of prolactin on urinary excretion and renal haemodynamics in conscious rats.

“…However, the reduction in inulin and PAH clearance observed in the present study persisted for only 1 hr. Miller & Van Gemert (1976) used a single 4 hr urine collection period and so any haemodynamic change induced by prolactin may have been obscured. Although the urinary alterations observed in the present series of experiments could be due solely to the changes in renal haemodynamics, prolactin can also affect renal tubular function.…”