Vasopressin contamination as a cause of some apparent renal actions of prolactin.

The injection or infusion of NIAMDD prolactin (NIH P-S-10) into unanesthetized rats resulted in water and electrolyte retention with a large increase in urine osmolality but no effect on glomerular filtration rate. Since these effects on urine output were also observed in homozygous Brattleboro rats, the antidiuretic activity could not have caused by the release of endogenous antidiuretic hormone. Radioimmunoassay of NIH prolactin showed that it was contaminated with vasopressin (20 ng/mg of prolactin). By comparison, Sigma prolactin had no observed effect on urine excretion and contained very little vasopressin (2.5 ng/mg). It is concluded that some of the renal effects of prolactin have been reported in the literature may have been caused by the contaminating vasopressin.     

Atriopeptins in fluid and electrolyte homeostasis

Atriopeptins are biologically active peptides with potent natriuretic, diuretic, and vasorelaxant activities. Manipulation of an animal's salt and water intake influences the synthesis, storage, and release of atriopeptin. In addition to its direct effects on fluid and electrolyte balance, atriopeptin influences other volume regulatory hormones, including renin, aldosterone, and vasopressin. Atriopeptin, by its direct actions and its effects on hormone systems, provides a means for delicate hormonal control of fluid and electrolyte homeostasis.     

Antidiuretic action of prolactin in the rat with diabetes insipidus.

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 insulin 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 administration stimulates rat hepatic DNA synthesis

Prolactin is an important growth modulatory hormone in fetal and adult tissues. Its administration stimulates enzymatic markers of the G1 phase of cell cycle in rat liver and other tissues. To determine the effects of prolactin administration on hepatic DNA synthesis (S phase), rats received prolactin at 12 hour intervals for 48 hours and DNA synthesis was assessed by [3H]-thymidine incorporation. Prolactin administration stimulated DNA synthesis 2-4 fold above controls in the livers of adult and weanling animals. Increased incorporation of radiolabel was associated with the nucleus of hepatoparenchymal cells. These data support the hypothesis that prolactin may be a physiological regulator of hepatic DNA synthesis. Further, since stress stimulates prolactin secretion, we suggest that prolactin may participate in the hepatic compensatory hyperplasia elicited by the stress associated with partial hepatectomy.     

Neurohypophysial hormones and renal function in fish and mammals

The two major basic neurohypophysial peptides, arginine vasopressin (AVP) of mammals and arginine vasotocin (AVT) of all non-mammalian vertebrates, share common structure and major roles in regulating renal function. In this review the complexity of AVP actions within the mammalian kidney is discussed and comparisons are made with the emerging picture of AVT's renal effects in fish. It has become apparent that the antidiuretic action of the neurohypophysial hormones is an ancient phylogenetic phenomenon, although this is based upon reduced glomerular filtration in fish by comparison with predominant tubular effects in mammals. Nonetheless, there appears to be retention of AVP effects upon the functional heterogeneity of nephron populations in mammals. Preliminary evidence for the possible existence of V(2)-type (tubular) neurohypophysial hormone receptors in fish, implies possible AVT actions which parallel those in mammals on tubular ion transport. Further insight from recent mammalian tubule microperfusion studies suggests that in teleost fish both apical (tubular lumen) and basolateral (blood borne) AVT have the potential to modulate renal function, though this remains to be examined.     

Prolactin, fatherhood, and reproductive behavior in human males

Although humans are considered unusual among mammals for the intensity of care that fathers often provide offspring, little is known about the hormonal architecture regulating human paternal investment. Prolactin has important reproductive functions in both female and male mammals and other taxa, making it a candidate regulator of human paternal behavior. Notably, prolactin is higher during periods of offspring care in some species, but it is unknown if this pattern occurs in human fathers. We draw on a sample of men (n = 289; age 21-23 at baseline) from Metropolitan Cebu City, Philippines to evaluate relationships between prolactin, assayed from dried blood spots, and components of reproductive behavior and relationship status. In this sample, fathers had higher prolactin than nonfathers (P = 0.006), and fathers of infants had borderline higher prolactin than fathers of older children (P = 0.054). Among single nonfathers at baseline (2005), baseline prolactin did not predict who transitioned to fatherhood by follow-up 4.5 years later. Among nonfathers, men with greater prolactin reported more lifetime sexual partners (P = 0.050) as well as more sexual activity in the month before sampling (P = 0.060). Our results suggest that fathers in Cebu have higher prolactin than nonfathers, with hormone levels highest among fathers of young infants. Although these findings are generally consistent with evidence from other species for pronurturing effects of prolactin, evidence for positive relationships between the hormone and measures of sexual behavior at Cebu point to likely complexities in the hormone's involvement in male reproductive strategy.     

Activation of adenylate cyclase in renal medulla by bovine growth hormone. An artifact attributable to vasopressin.

The effect of bovine growth hormone on adenylate cyclase activity was studied in bovine and rat renal medulla. Highly purified growth hormone (lot B1003A) increased adenylate cyclase activity in plasma membranes from bovine renal medulla from 132+/-6 pmol cyclic AMP formed/mg protein per 10 min to 364+/-10 pmol cyclic AMP formed/mg protein per 10 min. Similar results were seen with homogenates of rat renal medulla. The minimum effective concentration of bovine growth hormone required to activate adenylate cyclase was 0.5 mug/ml and maximum activation was detected at 500 mug/ml. The amount of vasopressin determined by radioimmunoassay to contaminate the growth hormone caused an increase in adenylate cyclase activity comparable to that of the corresponding concentration of growth hormone that was tested. Dialysis of growth hormone and vasopressin resulted in parallel reductions in the effect of each hormone on adenylate cyclase activity. Similarly, both growth hormone and vasopressin produced increases in short circuit current in isolated toad bladders but these effects were not detectable after dialysis of the hormones. In contrast, the effect of growth hormone on the uptake of 35SO2-4 by cartilage from hypophysectomized rats was not decreased after dialysis. These results indicate that available preparations of growth hormone are contaminated by small but physiologically significant amounts of vasopressin and that the activation of adenylate cyclase activity in renal medulla in response to growth hormone can be explained by this contamination rather than by an effect of growth hormone per se.     

Localization of prolactin receptor in the dorsal and ventral skin of the frog (Rana ridibunda)

The dorsal and ventral skin in amphibians plays an important role in osmoregulation. Prolactin hormone is involved in regulation of amphibian skin functions, such as water and electrolyte balance. Therefore, amphibians may be useful as a model for determining the sites of the prolactin receptor. In this study, prolactin receptor was detected in frog dorsal and ventral skin using immunohistochemical staining method. Prolactin receptor immunoreactivity was localized in all epidermal layers except stratum corneum of dorsal skin epidermis, stratum germinativum layer of ventral skin epidermis, myoepithelial cells, secretory epithelium and secretory channel cells of granular glands in both skin regions. The mucous glands and secretory granules of granular glands did not show immunoreactivity for the prolactin receptor. According to our immunohistochemical results, the more widespread detection of prolactin receptor in dorsal skin epidermis indicates that prolactin is more effective in dorsal skin. Presence of prolactin receptors in epidermis points out its possible osmoregulatory effect. Moreover, detection of receptor immunoreactivity in various elements of poison glands in the dermis of both dorsal and ventral skin regions suggests that prolactin has a regulatory effect in gland functions.     

Vascular, renal, and endocrine responses to low-dose atrial natriuretic peptide in the fluid-balanced New Zealand genetically hypertensive rats with and without endogenous arginine vasopressin.

In hypertension, the relationship between atrial natriuretic peptide (ANP) and vasopressin (AVP) is not yet clear, although their renal actions are effectively autoregulation. To examine the possible interaction further, the responses to ANP infusion (75 ng x min (-1), i.v.) have been investigated in both hypertensive and normotensive AVP-replete (HT and NT) and AVP-deficient (HTDI and NTDI) rats. This study aimed to assess the renal function and the plasma hormone concentrations of AVP, angiotensin II (AII), ANP, aldosterone, and corticosterone in the conscious, chronically catheterized, fluid-balanced rats, and to examine the cardiovascular, renal, and endocrine responses to a constant infusion of a low-dose ANP. Data gained from the present study showed, for the first time, the hormone profile, plasma electrolyte composition, and detailed renal function of the servo-controlled, fluid-balanced rats. The similarities of plasma electrolyte composition between servo-controlled and untreated rats indicated that the servo-controlled fluid replacement technique maintained the differences between the strains and maintained body fluid balance during the experimental periods. Following ANP administration, there were no changes in glomerular filtration rate (GFR) in all groups, but an enduring diuresis and natriuresis were observed in HT and NT, which were milder in HTDI rats. However, the hypotensive effect of ANP was of a similar magnitude in all rat strains. HTDI rats exhibited an inhibition of the renin-angiotensin system (RAS), which may have participated in the reduced mean arterial blood pressure (MAP) and natriuresis observed in these rats. The renal actions of ANP appear to rely upon renal tubular events, as indicated by increased fractional electrolyte excretions in the AVP-replete rats. This study highlights the importance of AVP to the profile of the renal actions of ANP in normal rats.     

Osmotic and volume control of diuresis in conscious ducks (Anas platyrhynchos)

Summary In conscious Pekin ducks made diuretic either by infusing hyposmotic glucose solution or isosmotic saline, osmotic and volume effects on renal water excretion were investigated. As in mammals, antidiuresis mediated by enhanced release of antidiuretic hormone was induced by increasing carotid blood osmolality while a decrease augmented diuresis, indicating cerebral osmotic control of renal water excretion in birds.In contrast to the situation in mammals, a sensitive diuretic response to isosmotic volume expansion, corresponding to 1% of the extracellular volume, can be demonstrated, with intracarotid and intravenous application of the isosmotic saline infusion having identical effects.Volume loading with isosmotic saline produced a greater diuretic response than loading with the same amount of autologous blood, thereby indicating a major contribution of volume changes in the interstitial compartment to the control of renal water excretion. This corresponds to the importance of the interstitial fluid compartment for the control of salt gland activity in this species.Abbreviations AVP arginine vasopressin - ECF extracellular fluid - i.c., i.v. intracarotid, intravenous - ECFV ECF volume     

Involvement of the V2 Vasopressin Receptor in Adaptation to Limited Water Supply

Mammals adapted to a great variety of habitats with different accessibility to water. In addition to changes in kidney morphology, e.g. the length of the loops of Henle, several hormone systems are involved in adaptation to limited water supply, among them the renal-neurohypophysial vasopressin/vasopressin receptor system. Comparison of over 80 mammalian V2 vasopressin receptor (V2R) orthologs revealed high structural and functional conservation of this key component involved in renal water reabsorption. Although many mammalian species have unlimited access to water there is no evidence for complete loss of V2R function indicating an essential role of V2R activity for survival even of those species. In contrast, several marsupial V2R orthologs show a significant increase in basal receptor activity. An increased vasopressin-independent V2R activity can be interpreted as a shift in the set point of the renal-neurohypophysial hormone circuit to realize sufficient water reabsorption already at low hormone levels. As found in other desert mammals arid-adapted marsupials show high urine osmolalities. The gain of basal V2R function in several marsupials may contribute to the increased urine concentration abilities and, therefore, provide an advantage to maintain water and electrolyte homeostasis under limited water supply conditions.     

In vivo and in vitro effects of prolactin and growth hormone on lipid metabolism in a teleost, Anabas testudineus (Bloch)

Prolactin (PRL) has an important role in the regulation of water and electrolyte homeostasis in teleosts. The present study was designed to evaluate the role of PRL and GH on malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PDH) and isocitrate dehydrogenase (ICDH) in Anabas testudineus. Ovine prolactin significantly inhibited ME, G6PDH and ICDH activities when administered in vivo compared to vehicle treated controls. In vivo administration of PRL reversed the action of bromocryptine on enzyme activities. Ovine growth hormone in vivo also modified the effect of bromocryptine but not to the level of prolactin. Combined action of PRL+GH in vivo was most effective in keeping the enzyme activities at normal level after bromocryptine treatment. Prolactin in vitro also reversed the action of bromocryptine on enzyme activities, while GH in vitro failed to do so. Hence, prolactin seems to have an inhibitory effect on lipid metabolism in this teleost. Combined action of PRL+GH is more prominent in in vivo conditions at low PRL levels. Dopaminergic pathways may be involved in the control of prolactin and to some extent on growth hormone secretion.     

Polyamine requirement for prolactin action on macromolecular synthesis in the MCF-7 human mammary epithelial cell line

The actions of insulin, hydrocortisone, prolactin and growth hormone on the synthesis of macromolecules in MCF-7 cells was determined in a serum-free defined medium. The inclusion of the polyamine spermidine in the medium was shown to enhance the insulin stimulation of the rate of [3H]uridine incorporation into RNA in a manner similar to that demonstrated for hydrocortisone. Spermidine, in addition to insulin and hydrocortisone, was also essential for prolactin to manifest a stimulation of the rate of [3H]uridine incorporation; this effect of spermidine was optimal with spermidine concentrations between 1 and 5 mM. Prolactin also stimulated the rate of [3H]leucine incorporation into total cellular protein and into an isoelectrically precipitable (pH 4.6) phosphoprotein fraction. The actions of prolactin on total protein and phosphoprotein synthesis were only expressed if spermidine, in addition to insulin and hydrocortisone, was contained in the culture medium. All of the prolactin responses were observed employing physiological concentrations of prolactin. Specificity of the prolactin responses was established by demonstrating that porcine growth hormone had no effects on RNA or phosphoprotein synthesis in the MCF-7 cells.     

Activation of adenylate cyclase in renal medulla by bovine growth hormone: An artifact attributable to vasopressin

The effect of bovine growth hormone on adenylate cyclase activity was studied in bovine and rat renal medulla. Highly purified growth hormone (lot B1003A) increased adenylate cyclase activity in plasma membranes from bovine renal medulla from 132 ± 6 pmol cyclic AMP formed/mg protein per 10 min to 364 ± 10 pmol cyclic AMP formed/mg protein per 10 min. Similar results were seen with homogenates of rat renal medulla. The minimum effective concentration of bovine growth hormone required to activate adenylate cyclase was 0.5 μg/ml and maximum activation was detected at 500 μg/ml. The amount of vasopressin determined by radioimmunoassay to contaminate the growth hormone caused an increase in adenylate cyclase activity comparable to that of the corresponding concentration of growth hormone that was tested. Dialysis of growth hormone and vasopressin resulted in parallel reductions in the effect of each hormone on adenylate cyclase activity. Similarly, both growth hormone and vasopressin produced increases in short circuit current in isolated toad bladders but these effects were not detectable after dialysis of the hormones. In contrast, the effect of growth hormone on the uptake of ³⁵SO₄²⁻ by cartilage from hypophysectomized rats was not decreased after dialysis. These results indicate that available preparations of growth hormone are contaminated by small but physiologically significant amounts of vasopressin and that the activation of adenylate cyclase activity in renal medulla in response to growth hormone can be explained by this contamination rather than by an effect of growth hormone per se.     

Prolactin is an important regulator of intestinal calcium transport

Prolactin has been shown to stimulate intestinal calcium absorption, increase bone turnover, and reduce renal calcium excretion. The small intestine, which is the sole organ supplying new calcium to the body, intensely expresses mRNAs and proteins of prolactin receptors, especially in the duodenum and jejunum, indicating the intestine as a target tissue of prolactin. A number of investigations show that prolactin is able to stimulate the intestinal calcium transport both in vitro and in vivo, whereas bromocriptine, which inhibits pituitary prolactin secretion, antagonizes its actions. In female rats, acute and long-term exposure to high prolactin levels significantly enhances the (i) transcellular active, (ii) solvent drag-induced, and (iii) passive calcium transport occurring in the small intestine. These effects are seen not only in pregnant and lactating animals, but are also observed in non-pregnant and non-lactating animals. Interestingly, young animals are more responsive to prolactin than adults. Prolactin-enhanced calcium absorption gradually diminishes with age, thus suggesting it has an age-dependent mode of action. Although prolactin's effects on calcium absorption are not directly vitamin D-dependent; a certain level of circulating vitamin D may be required for the basal expression of genes related to calcium transport. The aforementioned body of evidence supports the hypothesis that prolactin acts as a regulator of calcium homeostasis by controlling the intestinal calcium absorption. Cellular and molecular signal transductions of prolactin in the enterocytes are largely unknown, however, and still require investigation.     

Responses of vasoactive hormones in congestive cardiac failure

Congestive cardiac failure causes activation of various neurohumoral responses that increase total peripheral resistance and promote salt and water retention. These effects increase blood pressure and organ perfusion in the short term, but ultimately cause further cardiac decompensation by increasing ventricular afterload and cardiac work. The role of the renin-angiotensin-aldosterone system and the catecholamines is partially understood, and blockade of these systems as a treatment of heart failure is now established. The role of vasopressin in heart failure is more controversial, but there is now compelling evidence that vasopressin may have important vasoconstrictor actions in addition to its fluid retaining properties. Atrial natriuretic factor is a newly described cardiac hormone released from the atrium. Atrial natriuretic factor causes natriuresis, diuresis, vasodilatation, suppression of thirst, and suppression of both renin and aldosterone. These actions largely counteract the effects of the renin-angiotensin system and vasopressin. Plasma atrial natriuretic factor has been reported to be markedly elevated in human and experimental heart failure, and may act to limit the neurohumoral response to reduced cardiac output. This review summarizes our understanding of the vasoactive hormones and reports experimental evidence supporting a pathophysiological role for vasopressin and atrial natriuretic factor in congestive cardiac failure.     

Integumentary Effects of Prolactin in the Lower Vertebrates

Prolactin was first known as a stimulator of mammary secretion.It has since been found to induce secretion in the sebaceousglands of the mammal as well. It likewise stimulates secretoryactivity in the avian cropsac and in the mucous glands of fishesand of amphibians when thyroid hormone is also present. Prolactinhas mitogenetic effects on a variety of structures includingthe amphibian stratum corneum and induces growth of the tailfin in larval anurans and in both larval and adult newts. Prolactincauses the regression of cornified tubercles in the skin ofthe newt yetsynergizes with androgen in the presence of thethyroid hormone to induce the formation of keratinized nuptialpads. A similar synergism between prolactin and steroidal hormonesproduces avian incubation patches. There is indication thatprolactin may facilitate the growth of hair in mammals but detailedinformation is lacking. Effects on pigmentation are attributedto prolactin in two fishes.     

Prolactin osmoregulatory function in fishes and its projection on mammals

Prolactin evolution and key role in fish osmoregulation were reviewed. Comparison of fish and mammalian prolactin was made in respect of its structure, producing tissues, regulation of pituitary secretion. Peculiarities of prolactin receptor structure and prolactin-induced signal cascades, tissue distribution and regulation of prolactin receptor expression were compared in fishes and mammals. Data on mechanisms of prolactin action on ionoconservation in teleost fishes at the level of gills, kidney, intestine, and skin were presented. The facts of prolactin participation in the regulation of water and salt balance in mammals were observed. The existence of fundamentally similar mechanisms of osmoregulatory prolactin action in fishes and mammals was accumed and algorithm of their investigation was suggested.     

The effects of immersion and exercise on prolactin during pregnancy

Prolactin is an important hormone during pregnancy, affecting mother, fetus, and amniotic fluid volume. Immersion is known to affect prolactin levels significantly. To determine the effect of immersion and exercise on the prolactin response during pregnancy, we examined serum prolactin levels at 15, 25, and 35 weeks' gestation and 10 weeks post partum. Twelve women completed 20 min land rest, 20 min immersion in 30 degrees C water to the xiphoid, and 20 min exercise in the water at 60% VO2max. Resting prolactin levels were 1.91 +/- 0.32, 4.55 +/- 0.5, and 5.85 +/- 0.27 nmol.l-1 +/- standard error of the mean at 15, 25, and 35 weeks' gestation, respectively. Postpartum lactating women had a resting mean prolactin level of 3.95 +/- 1.6 versus 0.22 +/- 0.4 nmol.l-1 in non-lactating women. Prolactin levels declined significantly during immersion even after correction for dilution by plasma volume shifts. The immersion response was inversely related to the duration of pregnancy with 29%, 22%, and 12% drops during 15-, 25- and 35-week trials, respectively. Compared to rest, exercise prolactin levels remained depressed during the 15th and 25th week trials. We hypothesize that immersion in water caused prolactin levels to decline.     

Expression of the long form of the prolactin receptor in magnocellular oxytocin neurons is associated with specific prolactin regulation of oxytocin neurons

Magnocellular neurons of the supraoptic (SON) and paraventricular nuclei (PVN) show considerable plasticity during pregnancy and lactation. Prolactin receptors (PRL-R) have been identified in both these nuclei. The aim of this study was to investigate the cell type(s) expressing mRNA for the long form of prolactin receptor (PRL-R(L)) and to determine whether patterns of expression change during pregnancy and lactation. In addition, we examined effects of prolactin on excitability of oxytocin and vasopressin neurons. Sections from brains of nonpregnant, pregnant, and lactating rats were hybridized with an 35S-labeled probe to label PRL-R(L) mRNA together with digoxigenin-labeled probes to detect either oxytocin or vasopressin mRNA. In the SON, PRL-R(L) mRNA was predominantly colocalized with oxytocin mRNA, with over 80% of oxytocin neurons positive for PRL-R(L) mRNA. Very few (<10%) vasopressin neurons expressed PRL-R(L) mRNA. In the PVN, PRL-R(L) mRNA was also predominantly found in oxytocin neurons, and the proportion of PRL-R(L)-positive oxytocin neurons increased significantly during pregnancy and lactation. As in the SON, relatively few vasopressin cells contained PRL-R(L) mRNA. For in vivo electrophysiology, nonpregnant rats were anesthetized, and then extracellular single neuron activity was recorded in identified oxytocin and vasopressin neurons. After a period of baseline recording, the effect of prolactin (1 microg i.c.v.) on firing rate was examined. Prolactin treatment of nonpregnant rats induced a significant decrease in firing rates of oxytocin neurons. There was no effect of prolactin on the activity of vasopressin neurons. Together, these data provide strong evidence that prolactin directly and specifically regulates activity of oxytocin neurons.