Effect of melatonin on salt gland and kidney function of gulls, Larus glaucescens.

This study examined effects of exogenous melatonin on osmoregulatory hormones and water and sodium secretion by salt glands and excretion via the kidneys of Glaucous-winged gulls (Larus glaucescens). Six saline acclimated gulls were injected with inulin and paraminohippuric acid and then infused with 500 mM NaCl to stimulate salt gland secretion. Each bird was given infusions of NaCl alone and NaCl plus melatonin. Experiments were made one week apart in a randomized order. A large blood sample (to measure osmoregulatory hormones) was taken before infusion, at secretion, and at the end of infusion. A small blood sample was taken at the midpoint of each of six 10 min sequential collections of salt gland secretion and urine. Melatonin tended to increase plasma sodium concentration, did decrease plasma osmolality, but did not affect potassium concentration. Melatonin did not affect salt gland secretion rate or concentration nor renal plasma flow or glomerular filtration. Melatonin increased urine flow rate, tended to increase urine sodium concentration, and did decrease urine potassium concentration. Combined renal and extrarenal sodium excretion was greater during MT treatment. During NaCl infusion, angiotensin II increased, aldosterone decreased, and arginine vasotocin remained unchanged. Melatonin did not affect these responses. These data suggest an osmoregulatory role for melatonin in birds with salt glands.

Influences of sex and saline intake on diurnal changes in plasma melatonin and osmoregulatory hormones of Pekin ducks (Anas platyrhynchos).

Melatonin (MT) inhibits salt gland secretion of Pekin ducks [Ching, A.C.T., Hughes, M.R., Poon, A.M.S., Pang, S.F., 1999. Melatonin receptors and melatonin inhibition of duck salt gland secretion. Gen. Comp. Endocrinol. 116, 229-240]. The present study examined simultaneous diurnal changes in plasma concentrations of MT and four osmoregulatory hormones of Pekin ducks to assess the possible interactions among these hormones that might contribute to inhibition of extrarenal salt secretion. The study compared diurnal changes in freshwater (FW) and saline-acclimated (SA) male and female ducks. We hypothesized plasma concentrations of osmoregulatory hormones: (1) differ between sexes (partially accepted); (2) vary diurnally (accepted, influenced by sex and treatment); (3) are correlated with MT (partially accepted); and their diurnal variation is affected by (4) sex (partially accepted); and (5) saline acclimation (partially accepted). We compared body mass, plasma osmolality (Osm(pl)), plasma volume, concentrations of plasma ions, and arginine vasotocin (AVT), angiotensin II (AII), prolactin, (PRL), and aldosterone (ALDO), in relation to plasma melatonin (MT). At night body mass increased in FW ducks and decreased in SA ducks. This likely reflects the higher plasma PRL concentration of female ducks and its middark increase only in SA ducks. Plasma volume increased at night in all but FW males. Plasma sodium and osmolality were higher in SA ducks and did not vary diurnally in either FW or SA ducks. Midday MT did not differ between males and females or between FW and SA ducks; at middark, all ducks, except FW females, increased MT. Midday AVT was higher in SA ducks. Only FW ducks increased AVT at middark. Changes in AVT and MT were positively correlated in males and negatively correlated in females. Males had higher AII and, at night, AII increased in SA ducks and decreased in FW ducks. AVT and AII were negatively correlated. ALDO was highly correlated with AII and unaffected by sex, saline, or time. At night, only AVT was elevated in FW ducks, while MT, AII, and PRL were elevated in SA ducks. FW and SA ducks appear to follow different, but equally effective, hormonal strategies to maintain osmotic homeostasis at night. We conclude that the effect of MT on salt gland secretion is probably a direct effect. These may be influenced by gender.

Changes in melatonin receptors in relation to the development of scoliosis in pinealectomized chickens.

STUDY DESIGN: The 2[125I]iodomelatonin binding assay was used to investigate the involvement of melatonin receptors in the development of scoliosis in pinealectomized chickens. OBJECTIVE: To compare the binding properties of melatonin receptors in the thoracic spinal cord between pinealectomized chickens that had scoliosis develop and those that did not. SUMMARY OF BACKGROUND DATA: Surgical pinealectomy in young chickens induced scoliosis with a reported incidence of 50% to 100%. The factors regulating the development of scoliosis in this animal model are unclear. Melatonin receptors have been shown in the spinal cord of chickens, but their functions are still unknown. This study addresses the question as to whether spinal cord melatonin receptors are related to the pathogenesis of scoliosis in pinealectomized chickens. METHOD: Control and pinealectomized chickens were kept under controlled lighting conditions and monitored for scoliosis development. At 9-11 weeks after pinealectomy, thoracic spinal cords were removed for 2[125I]iodomelatonin binding assay, and blood was collected for serum melatonin assay at either the middle of the light period or middle of the dark period. RESULTS: Pinealectomy in young chickens produced: (1) loss of diurnal variations in serum melatonin levels, (2) 50% incidence of scoliosis, and (3) attenuation in the diurnal variations in the receptor affinity to melatonin. No differences were detected in the serum melatonin levels or binding of spinal cord melatonin receptors between the pinealectomized chickens that had scoliosis develop and those that did not. CONCLUSION: Changes are detected in melatonin receptor binding after pinealectomy. However, these changes cannot account for the reason why scoliosis develops in some chickens after pinealectomy, while it does not in others. Neither low melatonin serum level nor changes in spinal cord melatonin binding can be a sole etiologic factor in the pathogenesis of scoliosis in pinealectomized chickens.

The effect of pinealectomy on scoliosis development in young nonhuman primates.

STUDY DESIGN: Prospective study on pinealectomy in primates. OBJECTIVE: To evaluate whether pinealectomy in a bipedal nonhuman primate model will result in the development of scoliosis. SUMMARY OF BACKGROUND DATA: Pinealectomy in newborn chickens consistently resulted in scoliosis development. Published data suggest that the surgical removal of the pineal, loss of melatonin secretion, and a bipedal posture are important elements in the development of scoliosis in lower animal models. METHOD: There were 18 rhesus monkeys between 8 and 11 months old that underwent pineal excision. All monkeys were kept in a regulated 12-hour light-dark cycle. Monthly radiographs assessed scoliosis development. Completeness of pineal excision was assessed by measurement of a major metabolite of melatonin in the urine, 6-sulfatoxymelatonin, using an enzyme-linked immunosorbent assay assessed. RESULTS: Mean follow-up was 28 months (range 10-41). Seven monkeys died prematurely, and 11 survived to date; the data from those that died could still be used, although follow-up was shortened. At the latest follow-up or death, scoliosis did not develop in any of the monkeys. Urinary 6-sulfatoxymelatonin measurements revealed 3 patterns. Group 1 consisted of 10 monkeys, which showed definite evidence of complete pineal excision. Group 2 consisted of an uncertain group of 2 monkeys in which the nighttime melatonin level is slightly high. Group 3 consisted of 6 monkeys that had incomplete pineal excision or ectopic melatonin production. CONCLUSIONS: To our knowledge, this is the first report of pinealectomy in nonhuman primates. Of the 18 monkeys, 10 had a loss of melatonin secretion, for a mean of 29 months after surgery. Because none of the monkeys had scoliosis develop, this study strongly suggests that the possible etiologic factors producing idiopathic scoliosis in lower animals are different from primates, and findings in lower animals cannot necessarily be extrapolated to human beings.

Effect of melatonin suppression on scoliosis development in chickens by either constant light or surgical pinealectomy.

STUDY DESIGN: This study was designed to compare the effect of suppression of melatonin secretion by bright light in chickens with that of surgical pinealectomy. OBJECTIVE: To determine whether suppression of melatonin secretion without surgery in chickens can result in scoliosis development. SUMMARY OF BACKGROUND DATA: Pinealectomy in chickens consistently produces scoliosis with anatomic characteristics similar to those of human idiopathic scoliosis. Conversely, cutting of the pineal stalk without removal of the pineal gland will also result in scoliosis. This study addresses the question of whether constant bright light can induce scoliosis formation, because it is well known that 24-hour bright lighting conditions can suppress the secretion of melatonin to an equivalent level as pinealectomy. MATERIALS AND METHOD: Seventy-seven newborn Nihon chickens were separated into three groups. A control group (n = 21) with no surgery performed; a pinealectomy group (n = 15) that served as surgical controls; and a constant light group (n = 41). The first two groups were kept together in a strict 12-hour light-dark cycle, whereas the third group was separately kept with constant lighting conditions (>100 lux). All the chickens were radiographed at two weekly intervals, and blood was taken during the middle of the light and dark cycles for serum melatonin assay using ELISA. RESULTS: Fifty-four percent of the pinealectomized chickens had scoliosis develop by 6 weeks. None of the constant-light chickens or controls had scoliosis develop for up to 11 weeks. Measurements of serum melatonin levels of the constant light group confirm that secretion is suppressed. CONCLUSION: This study suggests that for scoliosis to develop in chickens, the surgical operation itself is important and challenges the role of melatonin as an isolated etiological factor in the development of scoliosis.

mt(1) Receptor-mediated antiproliferative effects of melatonin on the rat uterine antimesometrial stromal cells.

It has been shown that melatonin regulates uterine function. Our previous studies have demonstrated the presence of melatonin receptors in the rat uterine endometrium, indicating that melatonin may act directly on the uterus. In the present study, the histological localization of the rat uterine melatonin binding was revealed by autoradiography and the molecular subtyping was studied by in situ hybridization in the stromal cells. The signal transduction process and effects of melatonin on stromal cell proliferation was also investigated. Our autoradiograms showed that 2[(125)I]iodomelatonin binding sites were localized in the antimesometrial endometrial stroma. In situ hybridization with specific mt(1) receptor cDNA probe in the primary culture of antimesometrial stromal cells demonstrated the expression of mt(1) receptor mRNAs. Melatonin dose-dependently inhibited forskolin-stimulated cAMP accumulation, which was reversed by pertussis toxin. This indicates that the rat uterine melatonin receptors are negatively coupled to adenylate cyclase via pertussis toxin sensitive G(i) protein. Melatonin also inhibited the incorporation of [(3)H]thymidine in the rat uterine antimesometrial stromal cells, showing that melatonin has an anti-proliferative effect on the uterus. Our results suggest that melatonin may act directly on the mt(1) melatonin receptors in the rat uterine antimesometrial stromal cells to inhibit their proliferation. Its action may be mediated through a pertussis toxin-sensitive adenylate cyclase coupled G(i)-protein.