Developmental changes in male Siberian hamsters (Phodopus sungorus) exposed to different gestational and postnatal photoperiods

In Siberian hamsters, juvenile somatic and reproductive development is influenced by the photoperiods experienced both during gestation and after birth. On the day of parturition, parents and young were transferred from either 16L (16 hr of light and 8 hr of darkness/day) or 10L to one of the three photoperiods (14L, 12L, and 10L), and on postnatal day 27 male juveniles were either pinealectomized or sham-operated. At various intervals from postnatal days 27-330, the following parameters were determined: body weight, testis size, pelage type, serum concentrations of follicle-stimulating hormone (FSH) and prolactin (PRL). A postnatal photoperiod <14L was required to initiate delayed pubertal development followed by an eventual 'spontaneous' achievement of body weight, testis size, pelage, and serum FSH and PRL levels characteristic of adult, long-day males. The data suggest that serum FSH 'surges' in the pineal-intact hamsters are associated with spontaneous testicular development regardless of gestation photoperiod. The results also indicate that gestational photoperiod affects the timing of the molt to winter-type pelage and its eventual spontaneous development in pineal-intact hamsters that are exposed to short photoperiod following birth. Finally, our observations suggest that the interval timer that operates during prolonged short-day exposure to ultimately trigger a transition to the summer-type physiology may begin to function before birth in the offspring of females exposed to short photoperiod during gestation.     

Sexually Dimorphic Effects of Melatonin on Prolactin Cell Function in Male and Female Syrian Hamsters

The purpose of this study was to determine and compare the effects of chronic melatonin treatment in vivo on several aspects of prolactin (PRL) cell activity (PRL synthesis, storage, and release) in vitro in male and female Syrian hamsters. Adult male and female hamsters were maintained on long photoperiod and treated with daily late afternoon injections of melatonin (25 micrograms) or vehicle for 11 weeks. Melatonin treatment resulted in an 85% and 65% decrease in serum PRL levels in male and female hamsters, respectively. There was a similar 79% and 64% decrease in PRL release in vitro from pituitaries of male and female hamsters respectively, treated with melatonin in vivo. Total stored PRL was 75% lower in male hamsters and 62% lower in female hamsters receiving melatonin. The synthesis of PRL by pituitaries from melatonin-treated male hamsters was reduced by 65%, whereas in melatonin-treated females it was decreased by 58%. Both nanomolar and micromolar doses of melatonin in vitro caused a modest but significant decrease (14-19%) in the amount of PRL stored in and released from normal male pituitaries without affecting synthesis. The inhibitory effects of melatonin on PRL cell function appear to be more pronounced in male than in female hamsters suggesting a sexually dimorphic response to this pineal hormone. While melatonin's PRL-inhibitory effects appear to be exerted primarily via indirect neuroendocrine mechanisms, a secondary component of its overall regulation of PRL processing may involve direct pituitary mechanisms as well.     

Influence of prenatal photoperiod on postnatal plasma concentrations of progesterone and prolactin in female red deer (Cervus elaphus) reared in constant equatorial photoperiod

Abstract: Prenatal photoperiod influences postnatal prolactin secretion and the timing of reproductive development in male red deer reared from birth in a constant equatorial photoperiod (12: 12 light: dark). The present trial investigated whether a similar phenomenon occurs in female red deer. Female deer whose mothers had been exposed for the last 14 weeks of gestation to long (group L, 18: 6 light: dark) or short day length (group S, 6: 18 light: dark) were kept from birth in constant equatorial day length with food available ad libitum. Both groups showed similar live-weight gain to 90–100 weeks of age. Blood samples taken once or twice weekly were analyzed for progesterone and prolactin. Progesterone concentrations indicated that there was no difference between the groups in the timing of the first incidence of ovarian (luteal) activity, which occurred at a normal or late age for natural puberty (67 weeks or older). Only one individual per group exhibited normal repeated luteal cyclicity since there was a high incidence of irregular or abnormal luteal function. Plasma prolactin concentrations at birth were higher in group L than group S (P < 0.001). Thereafter, although the mean and peak values did not differ significantly between the groups, there was a significant difference in the pattern of secretion; deer in group L showed significant clustering of prolactin peaks (P < 0.01) at a mean age of 48 weeks, whereas deer in group S showed a random distribution of peaks. Therefore, for female red deer raised in constant equatorial photoperiod, prenatal long day lengths did not advance timing of puberty. However, the long-term pattern of prolactin secretion tended to be synchronized by long but not by short day lengths experienced prenatally.     

Diurnal changes in the content of indoleamines, catecholamines, and methoxyindoles in the pineal gland of the Djungarian hamster (Phodopus sungorus): Effect of photoperiod

Abstract: Early investigations of the effect of sleep deprivation on plasma melatonin reported no major changes. Recently, 36 hrs of sleep deprivation was reported to elevate melatonin levels on the post-sleep deprivation night. Given these contradictions melatonin, Cortisol, prolactin, and thyroid stimulating hormone before, during, and, after sleep deprivation were examined in nine healthy young males following one night of sleep deprivation. Hormone levels at hourly intervals, for each night, were statistically analyzed by a repeated measures, two-way factorial ANOVA. ANOVA was also performed for measures of area under the curve (AUC). No significant differences were observed for melatonin levels. Cortisol was significantly higher on the sleep deprivation night presumably reflecting the aroused state accompanying being awake; however, there were several time points on the control night when it was elevated also. Prolactin was higher on the post-sleep deprivation and control nights but did not rise on the deprivation night, indicating a useful nonpolysomnographic index for discriminating overnight sleep and awake states. TSH levels showed a similar rise during the control and sleep deprivation nights, but remained flat on the post-sleep deprivation night. It appears that the pineal is insulated against feedback from changes to the level of arousal accompanying sleep and wakefulness. In comparison, Cortisol, prolactin, and TSH levels vary with these states and are, therefore, useful indices of arousal and sleep-wake.     

Calmodulin and a cyclic nucleotide-dependent protein kinase facilitate the prolactin-induced increase in tyrosine hydroxylase activity in tuberoinfundibular dopaminergic neurons

Many aspects of tuberoinfundibular dopaminergic neuronal function are increased by elevated prolactin (PRL) levels, including the activity of tyrosine hydroxylase, the rate-limiting enzyme in the biosynthesis of dopamine. This study evaluated the roles of calmodulin, cyclic nucleotide-dependent protein kinase, and calcium/calmodulin-dependent protein kinase II in the PRL-induced increase in tyrosine hydroxylase activity. Ovariectomizerd rats were treated with haloperidol or ovine PRL (oPRL) for 20–30 h before the experiment, respectively. Treatment with haloperidol increased circulating PRL levels 8-fold and tyrosine hydroxylase activity in the stalk-median eminence 1.8-fold. Treatment with oPRL increased tyrosine hydroxylase activity 1.9-fold. W-7, a calmodulin antagonist, reversed both the haloperidol- and oPRL-induced increase in tyrosine hydroxylase activity to control levels. H-8, a cyclic nucleotide-dependent protein kinase inhibitor, also reversed the haloperidol induced increase in tyrosine hydroxylase activity. KN62, a selective calcium/calmodulin-dependent protein kinase II inhibitor, attenuated the haloperidol-induced increase in tyrosine hydroxylase activity, but KNO4, a structurally related control compound, had no effect. By contrast, the oPRL- and haloperidol-induced increases in tyrosine hydroxylase activity were not altered by KN93, a selective calcium/calmodulin-dependent protein kinase II inhibitor. These data indicate that calmodulin and a cyclic nucleotide-dependent protein kinase contribute to the PRL-induced increase in tyrosine hydroxylase activity, but the role of calcium/calmodulin-dependent protein kinase II is still unclear.     

Minireview The influence of season, photoperiod, and pineal melatonin on immune function

Abstract: In addition to the well-documented seasonal cycles of mating and birth, there are also significant seasonal cycles of illness and death among many animal populations. Challenging winter conditions (i.e., low ambient temperature and decreased food availability) can directly induce death via hypothermia, starvation, or shock. Coping with these challenges can also indirectly increase morbidity and mortality by increasing glucocorticoid secretion, which can compromise immune function. Many environmental challenges are recurrent and thus predictable; animals could enhance survival, and presumably increase fitness, if they could anticipate immunologically challenging conditions in order to cope with these seasonal threats to health. The annual cycle of changing photoperiod provides an accurate indicator of time of year and thus allows immunological adjustments prior to the deterioration of conditions. Pineal melatonin codes day length information. Short day lengths enhance several aspects of immune function in laboratory studies, and melatonin appears to mediate many of the enhanced immunological effects of photoperiod. Generally, field studies report compromised immune function during the short days of autumn and winter. The conflict between laboratory and field data is addressed with a multifactor approach. The evidence for seasonal fluctuations in lymphatic tissue size and structure, as well as immune function and disease processes, is reviewed. The role of pineal melatonin and the hormones regulated by melatonin is discussed from an evolutionary and adaptive functional perspective. Finally, the clinical significance of seasonal fluctuations in immune function is presented. Taken together, it appears that seasonal fluctuations in immune parameters, mediated by melatonin, could have profound effects on the etiology and progression of diseases in humans and nonhuman animals. An adaptive functional perspective is critical to gain insights into the interaction among melatonin, immune function, and disease processes.     

Maternal transfer of photoperiodic information in Siberian hamsters. vi. effects of time-dependent 1-hr melatonin infusions in the mother on photoperiod-induced testicular development of her offspring

Abstract: We tested in Siberian hamsters the nature of the maternal signal that relays photoperiodic information to the developing fetuses. As previous investigations have identified maternal hormonal and circadian components in this process, the specific goal of this presentation is to determine quality of the signal that connotes daylength when it is imparted to the fetus. Does the function of the signal received by the fetus best support the coincidence or duration hypotheses of photoperiodic induction? Pregnant hamsters received 1 or 8 hr melatonin or vehicle infusions everyday. Juveniles of intact mothers gestated on 16 hr of light per day (16L) experienced maximal suppression of testicular development when reared on 14L. However, when intact mothers gestated on 10L received a 1‐hr melatonin infusion daily at 20:00–21:00 hr, their young responded to 14L with greatly accelerated testicular development. In the absence of the maternal pineal gland (and, therefore, the maternal melatonin signal), the effects of maternal melatonin infusions were reversed. Here, only the juveniles of 16L‐gestated females infused at 20:00–21:00 hr daily responded to 14L with enhanced testicular development. All other groups showed the same extent of gonadal development, independent of the time or type of infusion their mothers received. Testicular development on 14L of all juveniles from pinealectomized mothers gestated on 10L was of the same magnitude, regardless of the type and time of infusion their mothers received during pregnancy. The results suggest that the maternal signal transferred to the fetuses during gestation consists not only of the daily melatonin signal, but also some circadian‐based component that greatly affects the effect of the former. The timing, and not the duration, of the maternal melatonin signal with respect to the animals’ (mother and fetus) circadian day is of crucial importance in the transfer of photoperiodic information from mother to fetus.     

Components of the melatonin message in the response to photoperiod of the tammar wallaby (Macropus eugenii)

Female tammars experiencing long-day photoperiod (LD 15:9) are in a reproductive state termed seasonal quiescence. After a change to LD 12:12, a sequence of endocrine events, dependent on a melatonin message being interpreted during the next 3 days, leads to the disappearance of a morning pulse of prolactin on day 4, and to reactivation of the quiescent corpus luteum by day 8. Elements of the message were investigated in three experiments. In experiment 1, tammars on LD 15:9 were injected with melatonin 2.5 hr before lights out on 0-5 successive days. All those receiving four or five daily injections, and six of ten receiving two or three injections, reactivated. In experiment 2, tammars on LD 15:9 were injected with melatonin or oil on 5 consecutive days to achieve a lengthening of the period of elevated melatonin from 9.0 hr to 9.5 hr, 10 hr, 10.5 hr, and 11.5 hr respectively. One of five tammars experiencing 10 hr and seven of ten experiencing the longer periods reactivated. In experiment 3, tammars on LD18:6 received melatonin 6 hr, 6 + 3 hr or 3 hr before lights out for ten successive days. Between injections the melatonin concentrations returned to basal levels. The treatments thus provided a skeletal increase in the profile of melatonin from 6 to 9 hr or 6 to 12 hr. All those treated at 6 + 3 hr reactivated and three of five treated at 6 hr only reactivated. We conclude that the tammar stores information about the change in the maximum duration of elevated melatonin experienced each night and, after three successive periods in which the duration is greater than 10.5 hr, it reactivates. Since reactivation cannot occur until completion of the third dark phase, the processing center must be active during the fourth day, prior to the abolition of the prolactin peak.     

Rhythmic Melatonin Response of the Syrian Hamster Pineal Gland to Norepinephrine In Vitro and In Vivo

Norepinephrine (NE, 10(-6) M) stimulated melatonin accumulation in the incubation medium of rat (but not Syrian hamster) pineals taken at the end of the light phase. However, NE elevated melatonin accumulation in the medium of pineals taken after 20 min of light exposure of animals of either species at 6 h into the 10-h dark phase. A dose response to 10(-7)-10(-5) M NE was observed in both the medium and pineals upon incubation of pineals taken from rats at 4 h into the light phase and from hamsters after 20 min light exposure at 6 h into the dark phase. Approximately 95% of the melatonin present was in the medium. The incubation time was 4 h in all cases. Subcutaneous injection of 1 microgram/g NE (either at the end of the light phase or after 30 min of light at 6 h into the dark phase) did not stimulate in vivo Syrian hamster pineal melatonin content determined 1 or 2 h after injection, whether the hamsters were placed in light or darkness after the injection. However, after 30 min of light beginning at 6 h into dark, injection of 5 micrograms/g desipramine (DMI, a blocker of catecholamine uptake into nerve endings) allowed a dramatic hamster pineal melatonin response to additional injection of 1 microgram/g NE, observed at 1 and 2 h in light after injection. A small effect of DMI alone was seen. DMI also potentiated the effect of NE (each 10(-6) M) on melatonin accumulation in the medium of incubated hamster pineals taken after a short light exposure at night. No significant stimulatory effect of NE and/or DMI was seen in vivo or in vitro near the middle of the light phase. Measurement of melatonin in the incubation medium is a useful method for studying pineal function. The Syrian hamster pineal has rhythm of sensitivity to NE (sensitivity evident at night) and even at night is protected by neuronal uptake from circulating NE-induced stimulation of melatonin production. NE appears to be the neurotransmitter for stimulation of pineal melatonin production in the Syrian hamster. The sensitivity rhythm and uptake protection might provide specificity of control of the nightly melatonin signal by reducing the chance of a melatonin response during the day or a response to circulating catecholamines from general sympathetic stimuli.     

Decreased expression of fos-related antigens (FRAs) in the hypothalamic dopaminergic neurons after immunoneutralization of endogenous prolactin

In our previous studies we found that administration of exogenous prolactin increased dopamine turnover in the terminal areas of the hypothalamic dopaminergic neurons controlling prolactin secretion from pituitary lactotrophs. In this study we investigated the effect of immunoneutralization of endogenous prolactin on the expression of FRAs in the tuberoinfundibular dopaminergic (TIDA), tuberohypophysial dopaminergic (THDA), and periventricular hypothalamic dopaminergic (PHDA) subpopulations of the hypothalamic dopaminergic neurons. Female rats were ovariectomized on d 0 of the experiment. At 1000 h of d 10, all animals were injected with 20 μg of 17-beta-estradiol sc to induce a proestrous-like surge of prolactin at 1700 h the next day. At 1000 h on d 11, half of the animals were injected with 200 μL of rabbit anti-rat prolactin antiserum ip, while the controls received normal rabbit serum. Groups of animals were sacrificed for immunocytochemistry in 2 h intervals between 1300 and 2100 h. Double-label immunocytochemistry for FRAs and tyrosine hydroxylase (TH) was performed and the results are presented as percentage of TH-immunoreactive neurons expressing FRAs. In the control animals, expression of FRAs decreased at 1500 h, gradually increased by 1900 h, but was lower than the basal levels by 2100 h. Expression of FRAs was significantly lower at 1900 h in the PHDA, THDA and TIDA neurons of prolactin antiserum treated rats than in the controls. These results indicate that elimination of endogenous prolactin from the circulation lowers the activity and/or prevents the reactivation of neuroendocrine dopaminergic neurons at the beginning of the dark phase.     

Effect of various acute 60 Hz magnetic field exposures on the nocturnal melatonin rise in the adult Djungarian hamster

ABSTRACT: Acute exposure to a 1 Gauss 60 Hz magnetic field for 15 min beginning 2 hr before darkness delays and blunts the nighttime melatonin rhythm in some but not all studies. To determine whether other exposure parameters (dose, mode, or time) influence the nocturnal melatonin rise, adult Djungarian hamsters reared in long days (16L: 8D, lights off at 1000–1800 hr) were acutely exposed to a 60 Hz continuous magnetic field (15 min of 1 or 0.1 Gauss) beginning 4 hr before or 4 hr after lights off. Other hamsters were exposed to a 60 Hz intermittent magnetic field (15 or 60 min of a 1 Gauss field, 1 min on then 1 min off) between 1 and 2 hr before lights off. In sham-exposed controls, i.e., hamsters simultaneously placed in an adjacent coil system but without current, pineal and serum melatonin concentrations increased from a low baseline (1 hr after lights off) to concentrations that were typical of the nighttime peak by 3 hr after darkness. Acute exposure to the 0.1 or 1 Gauss continuous magnetic field for 15 min at either 4 hr before or 4 hr after lights off did not disrupt the nocturnal rise in pineal or serum melatonin. Similarly, onset of the melatonin rhythm was not suppressed by intermittent magnetic field exposures compared to that in sham controls. Thus, several magnetic field exposure paradigms failed to alter the rising phase of the melatonin rhythm in pineal gland content or in circulation. These findings indicate that the biological clock mechanism that mediates photoperiodic time measurement in this seasonally breeding rodent is resistant to a variety of acute continuous or intermittent magnetic field exposures.     

Circannual reproductive rhythm in the European hamster (Cricetus cricetus): demonstration of the existence of an annual phase of sensitivity to short photoperiod

In the European hamster (Cricetus cricetus) short photoperiod (SP) is responsible for the transition between the breeding and the resting season and data obtained previously suggest that a circannual "clock" drives the annual rhythm of reproduction. This hypothesis implies the existence of a SP-sensitive phase of the circannual system that occurs independently of the photoperiodic regime perceived by the animals after their arousal from hibernation at the end of March. In control animals kept outside, testicular atrophy occurs in August. When the animals were transferred from outdoors to controlled SP conditions (LD 10:14 and ambient temperature Ta = 18+/-2 degrees C), immediately (Group II) or 2, 4, 6 wk after capture (Groups IV, V, VI, respectively), sexual arrest occurs at the same time between mid-June and mid-July. In the other groups, transfer from outdoors to SP either after 6, 8, 10, 12 or 14 wk (Groups VI, VII, IX, X, XI, respectively) after capture, is followed directly within 4 wk by the gonadal atrophy. When SP was applied from the beginning of August (Group XII) gonadal atrophy was observed after only 2 wk. In this last group, however, the rapid involution is the consequence of the already initiated decline in sexual activity induced by the short daylengths from July. When comparing the effect of SP in two different ambient temperatures (Ta: 18+/-2 degrees C vs 7+/-2 degrees C), immediately (Groups II vs III), 8 (Groups VII vs VIII) or 16 (Groups XII vs XIII) wk after capture, it appears that low temperature does not affect the physiological process described above. In the European hamster, after the gonadal regrowth at the end of hibernation, the animals do not need to experience increasing long days to react against SP. Gonadal inhibition is induced when, following our hypothesis, SP coincides with an endogenous period of sensitivity that extends from mid-May to at least July-August. The present findings complement and extend earlier evidence to support the existence of an endogenous circannual control of seasonal reproduction in the European hamster.     

A test of the coincidence and duration models of melatonin action in Siberian hamsters: the effects of 1-hr melatonin infusions on testicular development in intact and pinealectomized prepubertal Phodopus sungorus

The pineal hormone melatonin is known to play an important role in mediating photoperiodic messages to the reproductive system in seasonal breeding animals. Our goal was to test, in a single experimental paradigm, two hypotheses that have been forwarded to describe how the circadian rhythm of pineal melatonin transmits photoperiodic information to the reproductive system: 1) induction, i.e., a short-day effect, occurs when secreted melatonin and a circadian rhythm of sensitivity to melatonin coincide in time; 2) induction occurs following exposure to elevated circulating melatonin levels for a prescribed duration. In order to determine the relative validity of these hypotheses, we investigated the testicular maturation response to 1-hr daily infusions of 10, 25, and 50 ng of melatonin in pinealectomized intact and prepubertal Siberian hamsters (Phodopus sungorus). Animals received, beginning on day 15 of life, programmed subcutaneous infusions of melatonin or vehicle at one of five time points (19:00-20:00, 20:00-21:00, 21:00-22:00, 24:00-01:00, and 03:00-04:00 hr) for 15 days. In animals gestated and raised in a long photoperiod (LD16:8 = 16L, where L is the duration of light in hours, and D that of dark), melatonin infusion right after lights off (20:00-21:00 hr) significantly retarded gonadal maturation; this dose was ineffective at other times tested. Doses of 10 and 25 ng melatonin were ineffective at all time points. Identical results were obtained in prepubertal hamsters gestated in a short photoperiod (LD10:14 = 10L) and raised in 16L; these results were independent of the presence or absence of the pineal gland. In animals gestated and raised in 10L, melatonin infusions failed to suppress testicular development beyond that induced by the photoperiod; testicular development was maximally suppressed in all groups. The results of these investigations are best explained under the experimental conditions employed here: 1) the photoperiodic gonadal response in juvenile Siberian hamsters is regulated by the coincidence in time of exogenously administered melatonin with an intrinsic rhythm of sensitivity to melatonin, which, under the constraints imposed by our experimental design, occurred at 20:00-21:00 hr; and 2) the duration of the melatonin signal alone, equal in all groups, cannot explain the results.     

Changes in pituitary prolactin levels of female hamsters as a function of age, photoperiod, and pinealectomy.

Exposure of intact female hamsters to light:dark cycles of 1 h light alternating with 23 h darkness (LD 1:23) led to involution of the reproductive organs, a drop in prolactin levels within the anterior pituitary gland, and hypertrophy of the intrascapular brown fat. All of these changes were prevented if the animals were pinealectomized. Pituitary prolactin levels in control hamsters maintained in LD 14:10 cycles also decreased during the 8 week experimental period. Pituitaries of hansters killed at the end of the experiment contained about four-fifths less prolactin than those necropsied at the beginning of the study.     

Neuropeptide W as a stress mediator in the hypothalamus

Neuropeptide W (NPW) was isolated and found to be an endogenous peptide ligand for the orphan receptors GPR7 and GPR8. Centrally administered NPW caused a dose-dependent increase in corticosterone levels in rats. This observation indicates that NPW may play an important role in the hypothalamic organization of the endocrine response to stress. We examined the effects of immobilization stress and cold exposure on NPW-containing neurons in the hypothalamus of the rat, using dual immunostaining for NPW and Fos. In addition, to analyze the function of NPW, we studied the effect of intracerebroventricular (icv) NPW administration on Fos protein accumulation in the brain. Double immunohistochemistry for NPW and Fos showed that the percentage of Fos expression in the NPW-immunoreactive cells of the perifornical nucleus was significantly increased by immobilization stress compared with that in nonstressed rats. Similarly, the results indicated that cold exposure activates NPW-immunoreactive neurons in the perifornical nucleus. An icv administration of NPW resulted in significant Fos expression in the paraventricular nucleus, as compared with saline-infused controls. These results suggest that NPW is related to stress-responsive signal transduction, and that NPW may modulate the hypothalamus-pituitary-adrenal axis.     

Immunocytochemical study of GnRH and GnRH-associated peptide in male Syrian hamsters as a function of photoperiod and gonadal alterations.

Hypothalamic luteinizing-hormone-releasing hormone (GnRH) and gonadotropin-releasing-hormone-associated peptide (GAP) biosynthesis and storage were estimated by immunocytochemistry in male golden hamsters maintained in different photoperiods. Intact or castrated male hamsters with subcutaneously inserted testosterone implants were exposed to long-day (14:10) or short-day photoperiods (10:14) for 4-8 weeks. Exposure to short photoperiod for 4 weeks, an interval characterized by a suppression of gonadotropin secretion but not gonadal regression, was associated with an increase in the number of GnRH- and GAP-immunoreactive cells in the diagonal band of Broca/medial septum. Furthermore, morphometric analysis revealed that these animals displayed significantly more GnRH but not GAP immunoreactivity in the median eminence as opposed to hamsters exposed to long-day photoperiods. In additional studies, gonadally regressed hamsters exposed to short day lengths for 8 weeks had equal numbers of GnRH cells as did the long-day controls. These patterns suggest that reproductive quiescence in golden hamsters is not the result of depletions of neuronal GnRH stores available for secretion.     

Estrogen receptor messenger RNA expression in rat hypothalamus as a function of genetic sex and estrogen dose

Previously, we showed that estrogen receptor (ER) messenger RNA (mRNA) levels are decreased in cells of the mediobasal hypothalamus of ovariectomized (OVX) female rats following an acute estradiol treatment. Here, we examined whether the level of ER mRNA remains depressed in the continued long-term presence of estradiol, and questioned if there is a systematic relationship between the concentration of estradiol and the decrease in ER mRNA level. OVX female rats were implanted for 2 weeks with silastic capsules containing various concentrations of estradiol. Tissue sections were hybridized with a [3H] single-stranded DNA probe prepared from the region of the rat ER complementary DNA corresponding to the steroid binding domain, and relative mRNA level was assessed by counting grains over cells in specific hypothalamic nuclei. Estradiol induced a dose-dependent decrease in ER mRNA levels. Message levels declined in the ventrolateral aspect of the ventromedial nucleus (VLVM) by 57% and in the arcuate nucleus by 62% at the highest hormone concentrations used. Thus, ER mRNA down-regulation in female rat hypothalamus exhibits orderly dose dependence at a time following hormone treatment which ensures the system is at steady state. A second study determined if there exist differences in basal levels of ER mRNA expression between castrated (CAS) females and males, and if estradiol can down-regulate ER mRNA levels in male hypothalamus. CAS rats of both sexes were exposed acutely to estradiol benzoate (EB) for different periods of time. Again, in females, EB significantly decreased ER mRNA levels in VLVM by 55% (18 h) and in the arcuate nucleus by 74% (18 h). Interestingly, control CAS males had significantly lower basal ER mRNA levels than OVX females (52% lower than female levels in VLVM; 56% in arcuate), suggesting a sex difference in constitutive expression levels. Moreover, EB failed to down-regulate significantly ER message levels in males. There was no significant effect of sex or EB treatment on ER mRNA levels in medial amygdala. Thus, the second study shows sex differences and brain-region specificity in hormonal regulation of ER mRNA. These findings show that differences in basal levels and regulation of ER mRNA could be a substrate for sex differences in ER concentrations in the hypothalamus of the rat, and further raise the possibility of sex differences in concentrations of nuclear proteins related to the control of ER gene expression.     

Problem-solving as a function of age sex and the role appropriateness of the problem content

The purpose of this study was to investigate problem-solving ability as a function of age, sex and problem content by using 20 problems chosen from the problem-solving literature. The problems were administered without time limits to 8 males and 8 females in each of three age groups: 20–30, 40–50, 60–70. Analysis revealed that only age influenced performance with the middle-age group scoring significantly higher thin the other groups. Analysis of the time required by each age group to solve the problems showed the young group required significantly less time than the other groups. Finally, the young group was seen to make more errors of commission while the older group made more errors of omission.     

Argument for a non‐linear relationship between severity of human obesity and dopaminergic tone

Alterations in the dopaminergic system have been implicated in both animal and human obesity. However, to date, a comprehensive model on the nature and functional relevance of this relationship is missing. In particular, human data remain equivocal in that seemingly inconsistent reports exist of positive, negative or even no relationships between dopamine D2/D3 receptor availability in the striatum and measures of obesity. Further, data on receptor availability have been commonly interpreted as reflecting receptor density, despite the possibility of an alternative interpretation, namely alterations in the basal levels of endogenous dopaminergic tone. Here, we provide a unifying framework that is able to explain the seemingly contradictory findings and offer an alternative and novel perspective on existing data. In particular, we suggest (i) a quadratic relationship between alterations in the dopaminergic system and degree of obesity, and (ii) that the observed alterations are driven by shifts in the balance between general dopaminergic tone and phasic dopaminergic signalling. The proposed model consistently integrates human data on molecular and behavioural characteristics of overweight and obesity. Further, the model provides a mechanistic framework accounting not only for the consistent observation of altered (food) reward–responsivity but also for the differences in reinforcement learning, decision‐making behaviour and cognitive performance associated with measures of obesity.