Biomedical subjects

M D Rollag

Publications and source records attributed to M D Rollag.

At least 37 records · Page 2Linked to original sources

PubMed1993

Pertussis toxin sensitive photoaggregation of pigment in isolated Xenopus tail-fin melanophores.

Direct illumination of Xenopus laevis tail-fin melanophores results in rapid, reversible translocation of intracellular pigment granules to a perinuclear location, an effect distinct from and opposite to the photodispersion of pigment found in melanophores isolated from Xenopus embryos. In this report we show that both pertussis toxin and dibutyryl-adenosine-3',5'-monophosphate block the ability of light to cause photoaggregation of pigment in cultured tail-fin melanophores, whereas dibutyryl-guanosine-3',5'-monophosphate is without effect.

Animals↗

PubMed1993

Pupil size regulation of threshold of light-induced melatonin suppression.

The capacity of pupil dilation to affect light-induced plasma melatonin suppression was tested by exposing human subjects with freely constricting or pharmacologically dilated pupils to either 50 (n = 6), 100 (n = 8), or 200 lux (n = 5) of white light presented over the entire visual field. Pupil dilation significantly enhanced low level white light-induced melatonin suppression over that elicited with freely constricting pupils. Although 100 and 200 lux white light exposures resulted in significant melatonin suppression over control (no light) conditions, the effects of 50 lux were not strong enough to demonstrate statistically significant suppression with six subjects. Linear regression did not reveal a systematic relationship between theoretical retinal illuminance in Trolands and magnitude of melatonin suppression. These results suggest that pupil diameter may be a factor in the effectiveness of light stimuli used to shift circadian rhythms or to treat seasonal depression or sleep disorders.

Adult↗

PubMed1992

Maternal transfer of photoperiodic information in Siberian hamsters. V. Effects of melatonin implants are dependent on photoperiod.

Photoperiodic information is transferred from female Siberian hamsters to their fetuses during gestation. Although maternal melatonin is known to be essential for the transfer of prenatal photoperiodic information, its specific role is not well defined. The duration of the daily melatonin signal, expressed as an elevation of serum melatonin levels in the maternal circulation, has been hypothesized to convey day length information to the fetus. If this hypothesis is valid, it predicts that identical maternal melatonin signals should affect the fetuses identically, regardless of the prenatal photoperiod. To test this hypothesis, adult females received melatonin in beeswax or beeswax alone. They were paired with males and housed in photoperiods of 12L:12D or 16L:8D. On the day of parturition, mother and young were transferred to constant light (LL). Young males were killed on Day 28 of life, and weights of testes were determined. Prenatal treatment with beeswax alone did not affect the nature of the signal transferred from mother to fetus; young gestated in 12L:12D and reared in LL developed small testes, while those gestated in 16L:8D had large testes. On the other hand, the effect of the prenatal melatonin treatment on postnatal testicular development in LL was inversely dependent on the prenatal photoperiod: testicular growth was stimulated in young gestated in 12L:12D, but inhibited in young gestated in 16L:8D. To verify that the melatonin pellets produced equivalent serum melatonin levels in adult females in 12L:12D and 16L:8D, unmated adult females were killed 6-10 wk after receiving melatonin pellets. Serum levels were elevated in both groups throughout the day and night.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

The protein-phosphatase inhibitor okadaic acid mimics MSH-induced and melatonin-reversible melanosome dispersion in Xenopus laevis melanophores.

The present study describes the ability of 315 nM okadaic acid to induce melanosome dispersion in cultured Xenopus laevis melanophores. This effect of okadaic acid is similar to that of a-melanocyte stimulating hormone (MSH) and can be reversed by melatonin treatment; it indicates that a member of the protein-phosphatase 1 or 2A families must be active for maintenance of the aggregated state. Higher concentrations of okadaic acid (1 microM) attenuate the response of Xenopus melanophores to melatonin leading to the hypothesis that melatonin action is mediated by the calcium/calmodulin activated phosphatase 2B. This hypothesis seems unlikely, however, since the calcium/calmodulin inhibitors TFP and W7 do not prevent melatonin-induced pigment aggregation, but instead induce aggregation on their own.

Animals↗

PubMed1990

Light-induced plasma melatonin suppression in seasonal affective disorder.

1. Subjects with seasonal affective disorder were exposed to 0, 500 and 1000 lux of white light for one hour beginning at 0300 hours. 2. Plasma samples were taken periodically and analysed for melatonin. 3. Plasma melatonin levels were suppressed by exposure to both 500 and 1000 lux light levels, suggesting that SAD patients show no neuroendocrine insensitivity to light but may show supersensitive responses to light.

Female↗

PubMed1989

Ontogenetic development of S-antigen- and rod-opsin immunoreactions in retinal and pineal photoreceptors of Xenopus laevis in relation to the onset of melatonin-dependent color-change mechanisms.

In Xenopus laevis Daud., the ontogenetic occurrence of two photoreceptor-specific proteins, S-antigen and rod-opsin, was investigated and correlated to the maturation of the neurohormonal effector system involved in melatonin-dependent color-change mechanisms. Tadpoles ranging from stage 12 to 57 (Nieuwkoop and Faber 1956) were fixed in Zamboni's or Bouin's solution. Frozen or paraffin sections of either total heads or dissected brains and eyes were prepared and treated with highly specific antisera against S-antigen and rod-opsin. In the retina, immunoreactive S-antigen and rod-opsin were first demonstrated in a few centrally located photoreceptors at stage 37/38. Photoreceptors of the peripheral (iridical) portions of the retina gradually became immunoreactive during further development. As in the retina, the first S-antigen-immunoreactive photoreceptors in the pineal complex appeared at stage 37/38. At this and all later stages investigated rod-opsin immunoreactivity was restricted to a few dot-like structures resembling developing pineal outer and inner segments. In most animals rod-opsin immunoreactivity was completely absent from the pineal complex. The analysis of retinal proteins with the immunoblotting technique (Western blot) revealed that the S-antigen antibody bound to a 48-kDa protein and the rod-opsin antibody to a 38-kDa protein. The body lightening reaction was determined with the aid of the melanophore index in larvae fixed in light or darkness, respectively. Aggregation of melanophore melanosomes in darkness (the melatonin-dependent primary chromatic response) first occurred at stage 37/38 when melanophores started to differentiate and became pigmented. These results indicate that in Xenopus laevis (i) the molecular mechanisms of photoreception develop simultaneously in retina and pineal complex; (ii) most pineal photoreceptors differ from retinal rods in that they contain immunoreactive S-antigen but essentially no immunoreactive rod-opsin; and (iii) the differentiation of phototransduction processes coincides with the onset of melatonin-dependent photoneuroendocrine regulation of color-change mechanisms.

Animals↗

PubMed1989

Age, photoperiodic responses, and pineal function in meadow voles, Microtus pennsylvanicus.

We tested whether juvenile males of Microtus pennsylvanicus were more sensitive than adults to the suppressive effects of short photoperiods. Voles were transferred to short photoperiods (10L:14D) at 20 or 80 d of age, and 60 d later (i.e. at 80 or 140 d) the animals were killed at intervals throughout the day and night. Pineal glands were collected for measurement of melatonin, and the testes were weighed. There were no differences in paired testicular weights of 80 and 140 d old animals held on long days (median testicular weights: 1,953 and 1,843 mg). In contrast, median testicular weights of voles held on short days were 504 and 1,112 mg, respectively, at 80 and 140 d of age; the testicular weights of both groups were significantly different from their age-matched controls (P less than .001, two-sample t-tests on log transformed data). The responses of the two age groups were compared by normalizing the individual values by the mean and variance of the respective long-day controls. This comparison suggests that the responsiveness to photoperiod decreases as the animals age (t-test, P = .01). Duration and amplitude of the nocturnal rise in pineal melatonin content were similar in differently aged animals. In two experiments, voles were injected daily with melatonin from 20 to 80 or 80 to 140 d of age. Melatonin-injected animals had smaller testes than did saline-injected controls (ANOVA: P = .01), and injections were more effective in the afternoon than in the morning (P = .01). Comparison of the effectiveness of short day and melatonin injections in juvenile and adult voles suggests that while short days inhibited testicular development of young animals more than it induced regression of adults, this decrease in responsiveness may involve factors other than alterations in the nocturnal pattern of melatonin production.

Aging↗

PubMed1989

Cerebrospinal fluid-contacting area of the deep pineal: effects of photoperiod.

The surface of the pineal recess of the Syrian hamster demonstrates three morphologically distinct zones that are classified as the peripheral, transitional, and central zones. The central zone is the most remarkable because of the number of distinguishable morphological specializations in this region that appear to indicate interaction between the cerebrospinal fluid (CSF) and associated ventricular structures and the deep pineal gland. CSF-contacting pinealocytes are present in the central zone and have a relatively indistinct ventricular surface except for the presence of surface blebs and pinealocyte processes that course on the surface of the deep pineal. Supraependymal neurons and neuronal processes appear to converge on the central zone, occasionally having presumptive terminals that are associated with the cells of the central zone. When the hamsters were maintained in a short photoperiod (LD 8:16), the CSF-contacting area of the pineal recess was significantly larger in those hamsters killed 2 hours before lights off compared to those killed 2 hours before lights on (P less than 0.01). There were no significant differences in the CSF-contacting area when comparing two groups of hamsters maintained in a long photoperiod (LD 14:10, killed 2 hours before lights on and lights off, respectively). There was statistically significant interaction (P less than 0.05) between the lighting cycle and the time of day of death on the appearance of CSF-contacting pinealocytes. The hamsters maintained in LD 8:16 had significantly reduced testicular weights when compared to those maintained in LD 14:10. The plasticity of the central zone and the associated CSF-contacting pinealocytes of the pineal recess of the hamster are evidence that this region demonstrates morphological changes that are dependent upon the physiological state of the animal.

Animals↗

PubMed1988

Daily rhythms of pituitary-ovarian function in the immature hamster are independent of adrenal and pineal influence.

In female hamsters, the daily rhythm of LH appeared on the 15th or 16th day after birth with a peak occurring at about 16:00 h (14L:10D, lights on 06:00 h). Progesterone concentrations increased and became rhythmic a few days later. In serum samples collected at 14, 16, 18, 20, 25, 30, 40 and 60-62 days of age between 13:00 and 23:00 h, significant rhythms of serum cortisol and corticosterone concentrations were not detected before 25 days of age; furthermore, the phase of the rhythms did not stabilize to the adult pattern until about 40 days of age. As in the adult, significant rhythms were present in both sexes and the levels of cortisol were greater than those of corticosterone. Injection of pig ACTH (50 i.u./kg body wt, i.p.) significantly increased serum cortisol by 10 days of age, but corticosterone did not respond until 25 days of age. Thus, for cortisol at least, the appearance of 24-h rhythms in the serum is probably not dependent on the ability of the adrenal to respond to ACTH. Ovariectomy had no effect on the late afternoon surge of serum cortisol; similarly, adrenalectomy of immature females did not abolish the surge of LH. Ovariectomy did not alter the daily rhythm of pineal melatonin content and pinealectomy had no effect on the daily afternoon surge of LH. These results demonstrate functional independence of circadian rhythms in the pituitary-gonadal axis and the pituitary-adrenal axis of the immature hamster and also independence of daily rhythms of pineal melatonin and pituitary release of LH.

Adrenal Glands↗

PubMed1987

Suppression of pineal melatonin in Peromyscus leucopus by different monochromatic wavelengths of visible and near-ultraviolet light (UV-A).

The purpose of this study was to examine the effects of monochromatic visible and near-ultraviolet radiation (UV-A) on pineal melatonin suppression in the white-footed mouse, Peromyscus leucopus. To this end, mice were entrained to a daily cycle of 8 h of light and 16 h of darkness. During the night when pineal melatonin contents were high, mice were individually exposed for 5 min to specific wavelengths of monochromatic light (10 nm half-peak bandwidths). Control animals received the same handling conditions but no experimental exposure. Pineal glands were collected from animals 18 min after the 5 min experimental exposure and were later assayed for melatonin content. In groups of animals exposed to equal photon densities (2.64 X 10(15) photons/cm2) of either 320, 340, 360, 500, or 560 nm, mean pineal melatonin content was significantly suppressed as compared to the unexposed control animals. The 640 nm wavelength (red) at the same photon density did not suppress pineal melatonin. These experiments are the first to demonstrate light-induced suppression of pineal melatonin in Peromyscus leucopus. In addition, these data reveal a novel finding: the suppression of pineal melatonin content by ultraviolet wavelengths as low as 320 and 340 nm.

Animals↗

PubMed1987

Pertussis toxin blocks melatonin-induced pigment aggregation in Xenopus dermal melanophores.

The molecular mechanism of action for the pineal hormone melatonin was explored by testing melatonin interaction with the components of the hormone-sensitive adenylate cyclase complex in a Xenopus dermal melanophore bioassay. Forskolin was employed to stimulate melanosome dispersion. The ability of melatonin to reverse forskolin-stimulated pigment dispersion was assessed, as was the effect of pertussis toxin on the ability of melatonin to aggregate dispersed pigment. Forskolin elicited dispersal of melanosomes in a dose dependent manner (EC50 = 12 nM) in meninges from stage 52-56 tadpoles of Xenopus laevis. Maximal pigment dispersion was obtained with 100 nM forskolin. Melatonin reversed this effect of forskolin (EC50 = 1.5 nM), causing pigment aggregation. Pertussis toxin blocked the melatonin-induced aggregation (EC50 = 358 ng/ml). Prior treatment of the melanophore containing meningeal explants with pertussis toxin results in blockade of melatonin induced pigment aggregation. A 41 kDa pertussis toxin substrate is found in explant homogenates treated with 32P-NAD and pertussis toxin. The availability of this substrate is reduced by prior treatment of intact explants with pertussis toxin and depletion of melatonin responsiveness corresponds to depletion of the 41 kDa substrate. Together, these data suggest that melatonin action upon amphibian dermal melanosomes is mediated by a system requiring a protein similar to the regulatory protein Ni used by mammalian cells to mediate the action of hormones which inhibit adenylate cyclase through a cell surface receptor.

Adenylate Cyclase Toxin↗

PubMed1987

Diurnal variation of cation pump enzyme activity in pineal and seven other rat brain regions.

Adult female Long-Evans rats were maintained on an automatically regulated artificial lighting schedule of light:dark (L:D) 14.5:9.5 for 12 wk. After sacrifice at 0630, 1130, 1600, 1800, 2000, 2200, 0230, or 0400, the pineals were removed, weighed, and assayed for N-acetyltransferase (NAT), melatonin, Mg++-paranitrophenylphosphatase (pNPPase), and K-pNPPase activity. The brains were quickly dissected into the following areas: cerebellum, superior colliculi, inferior colliculi, visual cortex, auditory cortex, sensorimotor cortex, and the hypothalamic area around the suprachiasmatic nucleus. These regions were weighed and 10% sucrose homogenates were prepared for determinations of protein, Mg++-pNPPase, and K+-pNPPase activity. Pineal melatonin rose over six-fold from 144 +/- 70 pg/gland at 1130 to 981 +/- 173 pg/gland at 0230. Similarly, pineal NAT activity rose over 11-fold, from 119 +/- 12 pmol/gland/h to 1315 +/- 232 pmol/gland/h at the same times. K+-pNPPase activity rose by about two-thirds, from 133 +/- 12.8 nmol/gland/h to 224 +/- 22.3 nmol/gland/h from 1600 to 0230. However, when expressed per mg protein, these differences in pNPPase activity were not significant. There were no significant daily rhythms discernible in any of the seven other brain regions across these times. We conclude that cation pump enzyme activity varies only slightly with time in the rat brain and pineal gland, in spite of definite daily rhythms of pineal melatonin and NAT activity.

4-Nitrophenylphosphatase↗

PubMed1987

The suppression of nocturnal pineal melatonin in the Syrian hamster: dose-response curves at 500 and 360 nm.

It has recently been shown that wavelengths in the near-UV range (UV-A, 320-400 nm) are capable of influencing pineal melatonin content in the hamster. The purpose of this study was to compare the capacities of monochromatic visible and UV radiation for suppressing nocturnal pineal melatonin. Groups of male Syrian hamsters adapted to a 14-h light, 10-h dark cycle (lights on, 1700-0700 h) were exposed to irradiances of 500 or 360 nm light for 5 min during their dark phase. Both wavelengths suppressed pineal melatonin in a dose-related manner. The resultant fluence-response curves were similar in shape, although their corresponding threshold irradiances were markedly different. The calculated ED50 values for 500 and 360 nm light were 0.022 microW/cm2 (1.66 X 10(13) photons/cm2) and 0.306 microW/cm2 (1.66 X 10(14) photons/cm2), respectively. These data show that the induction of a 50% depression of pineal melatonin requires 10 times the number of 360-nm photons compared to 500-nm photons at the level of the cornea. Despite this difference in sensitivity to wavelength, environmental irradiances of UV-A are well above the threshold for melatonin suppression in the hamster. These results thus demonstrate the importance of considering UV-A, in addition to the visible wavelengths, in the regulation of hamster pineal physiology.

Animals↗

PubMed1986

Maintenance of testicular function in Turkish hamsters: interaction of photoperiod and the pineal gland.

Adult male Turkish hamsters maintained testicular function when exposed to photoperiods of 15, 16, or 17 h of light per day. Photoperiods of less than 15 or greater than 17 h of light per day induced a rapid and complete testicular regression. As pinealectomy had been shown by others to induce testicular regression in long-day Turkish hamsters, we thought that regression on 18 or more h of light might be based on the inability of the pineal to generate a daily rhythm of melatonin in production and release. This proved not to be the case. Animals exposed to 14-18 and 20 h of light per day had a robust nocturnal melatonin rhythm.

Animals↗

PubMed1986

Sensitivity of adult male Djungarian hamsters (Phodopus sungorus sungorus) to melatonin injections throughout the day: effects on the reproductive system and the pineal.

Twenty-four groups of adult male Djungarian hamsters (Phodopus sungorus sungorus) housed on 16L:8D received daily injections of melatonin, each group at a different hour of the day. Injections (5 micrograms/0.1 ml ethanolic saline 1:10, s.c.) continued for 15 wk, after which the animals were killed and the testes weighed to assess the efficacy of the injections in causing testicular regression. Two periods of melatonin sensitivity were identified. The first was a single time point 5 min before lights on (0455 h). The second was a 5-h period throughout the late afternoon (1600-2100 h; lights out 2100 h). Regression was complete in the 1700- and 1800-h groups only. A few animals failed to respond or regressed very slowly in the 1900- and 2000-h groups, and in the 1600- and 2100-h groups only partial regression was observed after 15 wk of injection. There was no demonstrable effect of exogenous melatonin administration on the endogenous rhythm of pineal melatonin; the rhythm in injected hamsters was of identical duration and amplitude to that in uninjected controls on the same photoperiod.

Animals↗

PubMed1986

Near-ultraviolet radiation suppresses pineal melatonin content.

UV radiation (200-400 nm) is generally considered to be outside the range of visible illumination for mammals. The aim of this study was to determine if UV wavelengths can influence pineal physiology. Experiments on hamsters confirm that wavelengths as low as 305 nm are transmitted through the clear ocular media to the retina. Furthermore, low irradiances of broadband (340-405 nm) and monochromatic (360 nm) UV radiation are capable of suppressing high nocturnal levels of pineal melatonin in intact, but not blind, hamsters. These data indicate that the hamster eye and neuroendocrine system are able to detect and respond to near-UV wavelengths.

Animals↗

PubMed1984

Effect of acute light exposure upon melatonin content, NAT activity, and nuclear volume in the gerbil pineal complex.

This report describes the response of both the superficial and deep components of the gerbil pineal gland to a 30-min pulse of fluorescent light at the time of the nocturnal peak in pineal activity. When gerbils were maintained in a 14 h light:10 h dark photoperiod, mean melatonin concentrations in the superficial pineal gland ranged between 72 and 108 pg/gland during the day and first 4 h of darkness, rose to a peak of 399 pg/gland 7 h after lights out, then returned to basal levels at the expected time of light onset. Pineal melatonin contents were reduced to daytime values within 30 min after exposure of gerbils to fluorescent light at the time of the nocturnal peak. These changes in superficial pineal melatonin content reflected the circadian pattern in serotonin N-acetyltransferase (NAT) activity, as would be expected if NAT controls melatonin synthesis. In addition to the reductions in NAT and melatonin content induced by nocturnal photic stimulation, there was a 30% reduction in mean pinealocyte nuclear volume. A nocturnal elevation in melatonin content but not in NAT activity occurred in the deep pineal gland. Unlike the superficial pineal gland, the deep pineal gland did not demonstrate a response in melatonin content, NAT activity, or pinealocyte nuclear volumes upon exposure of gerbils to light at the time of the nocturnal peak in superficial pineal activity.

Acetyltransferases↗

PubMed1983

Development and melatonin content of the deep pineal gland in the Syrian hamster.

The morphological relationships between the superficial and deep pineal glands of neonatal Syrian hamsters are described at both light and electron microscopic levels. In addition, melatonin contents in the two glandular masses are compared throughout a 14 hr light:10 hr dark photoperiod in 20-day-old hamsters. It has been found that the pineal anlage begins to separate into deep and superficial components between the first and third postnatal days of life. Separation is usually complete by day 12. The fine structure of the deep gland is similar to that of the superficial gland throughout development. By the time of weaning (20 days of age), the young hamsters exhibit distinct nighttime elevations of melatonin in both the superficial and deep glands, the quantities in the deep gland being approximately 5% those of the superficial pineal. Like that of the superficial pineal, the rise in deep pineal melatonin content can be abolished by exposure of hamsters to light.

Animals↗