Availability of metabolic fuels controls estrous cyclicity of Syrian hamsters.

Food deprivation and weight loss inhibit ovulation and estrous behavior in Syrian hamsters. In the present experiments, lean hamsters were more susceptible to starvation-induced anestrus than fat hamsters. However, anestrus was not caused by changes in any dimension of body size per se, but instead by the availability of metabolic fuels. Simultaneous pharmacological blockade of both fatty acid oxidation and glycolysis inhibited reproduction, but, as long as one of these metabolic pathways could be used, estrous cycles continued. Thus, reproduction in female Syrian hamsters is sensitive to the general availability of oxidizable metabolic fuels.

Photoperiodic control of seasonal body weight cycles in hamsters.

Syrian (Mesocricetus auratus) and Siberian (Phodopus sungorus sungorus) hamsters exhibit seasonal changes in body weight mainly by altering their carcass lipid stores. These seasonal changes are triggered largely by the photoperiod. Although both species exhibit gonadal regression when exposed to short photoperiods ("winterlike") daylength), they show opposite body weight changes. Syrian hamsters gain weight, but Siberian hamsters lose weight following short photoperiod exposure. Syrian hamsters prepare for overwintering by increasing energy stored as carcass lipid. In contrast, Siberian hamsters decrease their metabolic mass and therefore require lower energy intake for energy maintenance. In Syrian, and perhaps Siberian hamsters the short day-induced weight changes are exaggerated by high fat diets. Both species show photoperiod-induced changes in body weight without changing their food intake, suggesting a metabolic basis for these effects. In Syrian hamsters, the obesity is not secondary to gonadal regression, whereas in Siberian hamsters, the decrease in body weight is independent of the gonads for males but may be dependent upon the gonads in females. The pineal gland and its hormone, melatonin, are important transducers of photoperiodic signals in hamsters. This is certainly true for Siberian hamsters, in which pinealectomy blocks the short day-induced body weight loss. In contrast, pinealectomy has little effect on short day-induced weight gain in Syrian hamsters. Nevertheless, in both species, the body weight and gonadal changes induced by short day exposure are mimicked by systemic administration of melatonin in long day-housed animals. Thus, for these two hamster species, the same hormone, melatonin, produces opposite effects on body weight but does so by affecting the same carcass component. The target sites of action for the effects of melatonin on body weight change, energy metabolism, and reproductive status are not known. However, the suprachiasmatic and paraventricular nuclei of the hypothalamus are potentially important sites of action. The target site(s) and mechanism(s) of action for the pineal/melatonin-independent effect of photoperiod on body weight in Syrian hamsters are also unknown. This photoperiodic response is highly unusual among mammals in that it is not pineal-dependent. Studies of the mechanisms underlying these body weight changes in Syrian and Siberian hamsters may provide fundamental knowledge about how environmental influences affect obesity and they may also provide insight into the various strategies for overwintering shaped by natural selection.(ABSTRACT TRUNCATED AT 400 WORDS)

Metabolic fuels and reproduction in female mammals.

A complete reproductive cycle of ovulation, conception, pregnancy, and lactation is one of the most energetically expensive activities that a female mammal can undertake. A reproductive attempt at a time when calories are not sufficiently available can result in a reduced return on the maternal energetic investment or even in the death of the mother and her offspring. Numerous physiological and behavioral mechanisms link reproduction and energy metabolism. Reproductive attempts may be interrupted or deferred when food is scarce or when other physiological processes, such as thermoregulation or fattening, make extraordinary energetic demands. Food deprivation suppresses both ovulation and estrous behavior. The neural mechanisms controlling pulsatile release of gonadotropin-releasing hormone (GnRH) and, consequently, luteinizing hormone secretion and ovarian function appear to respond to minute-to-minute changes in the availability of metabolic fuels. It is not clear whether GnRH-secreting neurons are able to detect the availability of metabolic fuels directly or whether this information is relayed from detectors elsewhere in the brain. Although pregnancy is less affected by fuel availability, both lactational performance and maternal behaviors are highly responsive to the energy supply. When a reproductive attempt is made, changes in hormone secretion have dramatic effects on the partitioning and utilization of metabolic fuels. During ovulatory cycles and pregnancy, the ovarian steroids, estradiol and progesterone, induce coordinated changes in the procurement, ingestion, metabolism, storage, and expenditure of metabolic fuels. Estradiol can act in the brain to alter regulatory behaviors, such as food intake and voluntary exercise, as well as adenohypophyseal and autonomic outputs. At the same time, ovarian hormones act on peripheral tissues such as adipose tissue, muscle, and liver to influence the metabolism, partitioning and storage of metabolic fuels. During lactation, the peptide hormones, prolactin and growth hormone, rather than estradiol and progesterone, are the principal hormones controlling partitioning and utilization of metabolic fuels. The interactions between metabolic fuels and reproduction are reciprocal, redundant, and ubiquitous; both behaviors and physiological processes play vital roles. Although there are species differences in the particular physiological and behavioral mechanisms mediating nutrition-reproduction interactions, two findings are consistent across species: 1) Reproductive physiology and behaviors are sensitive to the availability of oxidizable metabolic fuels. 2) When reproductive attempts are made, ovarian hormones play a major role in the changes in ingestion, partitioning, and utilization of metabolic fuels.

Cytoplasmic 17 beta-[3H]estradiol binding in rat adipose tissues.

Ovarian hormones, particularly 17 beta-estradiol, have important effects on body fat levels in rats, but it is not known whether 17 beta-estradiol can act directly on various fat depots to affect adiposity or whether these effects are entirely indirect (e.g. via food intake, exercise, or various metabolic actions). We have found high affinity, estrogen-specific macromolecular binding of 17 beta-[3H]estradiol in the cytoplasmic fraction of adipose tissues from ovariectomized rats. Saturation analysis indicates a Kd of 7.4 X 10(-10) M, and binding is inhibited by unlabeled 17 beta-estradiol or 11 beta-methoxy-17-ethynyl-1,3,5(10)-triene-3,17beta-diol (R2858) but not by progesterone, 5 alpha-dihydrotestosterone, or cortisol. 17 beta-[3H]Estradiol binding is virtually abolished by incubation with pronase but not with DNase or RNase, indicating that the binding macromolecule is probably a protein. Binding is seen in all adipose tissues studied, including abdominal, sc, and brown fat. Binding site concentration is highest in parametrial fat pads, followed by retroperitoneal, brown, omental, and inguinal depots. Binding is also seen in the cytoplasmic fraction of isolated parametrial adipocytes. These data indicate that the various adipose tissues might be estrogen target tissues in rats. Therefore, it is possible that estrogenic effects on body weight and composition could be mediated in part by direct estrogen action on adipose tissues.

Photoperiodic control of body weight and energy metabolism in Syrian hamsters (Mesocricetus auratus): role of pineal gland, melatonin, gonads, and diet.

The effects of photoperiod and the pineal hormone melatonin on the regulation of body weight and energy metabolism were examined in Syrian hamsters, Mesocricetus auratus. Short photoperiod-housed female and male hamsters showed increases in body weight gain, feed efficiency, carcass lipid, brown adipose tissue mass, and thermogenic capacity. These effects of short photoperiods were mimicked by afternoon melatonin injections to hamsters in long-day photoperiods and were exaggerated in hamsters fed high fat diets. To determine the role of the gonads in these effects, ovariectomized hamsters were treated similarly and found to exhibit changes in body weight and energy metabolism that were 80-90% of those in gonadally intact hamsters. The role of the pineal gland in short photoperiod-induced body weight gain was examined in sham-pinealectomized and pinealectomized hamsters. Short photoperiod-induced increases in body weight were seen in both pinealectomized and sham-pinealectomized hamsters. Thus, pinealectomy blocks the effects of short photoperiods on reproductive function and thyroid activity, but not on body weight regulation. These results suggest that the effects of short photoperiods on body weight and energy metabolism are mediated by multiple, redundant mechanisms involving decreases in gonadal hormone secretion, changes in melatonin secretion, and gonad- and pineal-independent changes. All of the effects of short photoperiods are exaggerated in hamsters fed a high fat diet. These changes may represent adaptive preparatory responses that enhance winter survival in Syrian hamsters.

Inhibition of estrous behavior by progesterone in rats: role of neural estrogen and progestin receptors.

Sexual receptivity can be induced in ovariectomized rats with sequential injections of 17 beta-estradiol-3-benzoate (EB; 2 micrograms sc) and progesterone given 24 h apart. If a high dose of progesterone is used, estrous behavior is followed by a period during which sexual receptivity cannot be reinduced with a second progesterone injection (sequential inhibition). We have examined the effects of a hormone treatment which causes a sequential inhibition on levels of estrogen and progestin receptors in the hypothalamus-preoptic area-septum of ovariectomized rats. In a preliminary experiment, a single injection of 2 micrograms EB caused a significant increase in the concentration of brain cell nuclear estrogen receptors, Peak levels were seen at 12-24 h and remained significantly elevated as long as 72 h after EB. In a second experiment, we found that 48 h after EB, brain cytoplasmic estrogen receptors were significantly depressed and nuclear estrogen receptors were significantly elevated. However, a single progesterone injection (5 mg, sc) 24 h after EB had no significant effect on either cytoplasmic or nuclear estrogen receptor levels. Forty-eight hours after EB, brain cytoplasmic progestin receptors were significantly elevated compared with oil-injected controls. In a third experiment, progesterone (5 mg, sc) given 24 h after EB reduced neural cytoplasmic progestin receptors to levels significantly below those of oil-injected controls at 48 h. These results are consistent with the suggestion that progesterone does not interact with neural estrogen receptors to inhibit lordosis in rats. Rather, we suggest that progesterone may induce a behavioral refractoriness to subsequent progesterone treatments, at least in part, by reducing the concentration of neural cytoplasmic progestin receptors.

Manipulations of metabolic fuel availability alter estrous behavior and neural estrogen receptor immunoreactivity in Syrian hamsters.

Decreases in metabolic fuel utilization caused by food deprivation, diabetes, or treatment with metabolic inhibitors have been shown to suppress steroid-induced estrous behavior in ovariectomized Syrian hamsters. These same manipulations also caused a decrease in the number of detectable estrogen-receptor immunoreactive (ERIR) cells in the ventromedial hypothalamus (VMH) and the adjacent area lateral to it (VLH) in ovariectomized hamsters. Forty-eight hours of food deprivation or treatment with pharmacological blockers of glycolysis (2-deoxy-D-glucose) and fatty acid oxidation (methyl palmoxirate) decreased the number of detectable ERIR cells in the VMH/VLH. However, neither inhibitor given alone was sufficient to affect the number of detectable ERIR cells in the VMH/VLH, even when given in much higher doses. Therefore, the number of ERIR cells in the VMH/VLH, like steroid-induced estrous behavior, responds only to a combination of glucoprivation and lipoprivation and not to either alone. The effects of metabolic fuel restriction are not due to a general suppression of neural ERIR, because food deprivation or treatment with 2-deoxy-D-glucose and methyl palmoxirate actually increased the number of detectable ERIR cells in the medial preoptic area (mPOA) and had no effect in the nucleus of the solitary tract. Lesions destroying the area postrema (AP) prevented the decrease in ERIR cells in the VMH/VLH and the inhibition of estrous behavior caused by fuel restriction. However, AP lesions did not alter the effects of metabolic inhibitors on ERIR in the mPOA. On the other hand, subdiaphragmatic vagotomy abolished the effects of metabolic inhibitors on mPOA ERIR, but did not affect either lordosis or VMH/VLH ERIR. These results suggest that the suppression of estrous behavior induced by metabolic fuel restriction is at least in part due to a decrease in the number of ERIR neurons in the VMH/VLH. In addition, the estrogen-sensitive neurons in the VMH/VLH and mPOA receive metabolic cues via different neural pathways. The AP, but not vagus nerves, is required for ERIR neurons in the VMH/VLH to detect fuel availability; the vagus nerves, but not the AP, are necessary for estrogen-binding neurons in the mPOA to detect visceral information.

Expression of Fos-like proteins in gonadotropin-releasing hormone neurons of Syrian hamsters: effects of estrous cycles and metabolic fuels.

In female mammals, reproduction is sensitive to the availability of metabolic fuels, and food deprivation has been shown to suppress pulsatile LH secretion, attenuate the preovulatory LH surge, and prevent ovulation. It has been suggested that food deprivation impairs fertility by reducing the secretion of GnRH by GnRH-producing neurons in the forebrain. A series of experiments tested this hypothesis by examining the effects of estrous cycles and manipulations of metabolic fuel availability on the expression of Fos-like proteins (Fos-IR) in GnRH-immunoreactive (GnRH-IR) neurons in the forebrain of Syrian hamsters. GnRH-IR neurons were detected in several areas, including the diagonal band of Broca (DBB), medial septum (MS), rostral medial preoptic area (mPOA), and caudal POA. In the more rostral regions (DBB and MS/mPOA), GnRH-IR neurons expressed Fos-IR almost exclusively on day 4 of the cycle, just after the preovulatory LH surge. However, in the caudal POA, GnRH-IR neurons expressed Fos-IR across the entire cycle, including days 1-3, when LH secretion is pulsatile. Food deprivation on days 1 and 2 of the cycle, which attenuates the LH surge and blocks ovulation in hamsters, significantly reduced the proportion of GnRH-IR neurons that expressed Fos-IR on days 2 and 4 (caudal POA) or only on day 4 (DBB and MS/mPOA). Suppression of fuel availability with insulin or 2-deoxy-D-glucose on day 1 of the cycle mimicked the effects of food deprivation and reduced the proportion of caudal POA GnRH-IR neurons that expressed Fos-IR. The results of these experiments suggest that in Syrian hamsters, there are separate populations of GnRH-IR neurons associated with pulsatile and surge modes of LH secretion. In addition, the fact that manipulations of metabolic fuel availability cause changes in the expression of Fos-IR in both populations of GnRH-IR neurons provides strong support for the hypothesis that nutritional infertility is due in part to decreased GnRH secretion.

Effects of interscapular brown adipose tissue denervation on body weight and energy metabolism in ovariectomized and estradiol-treated rats.

Ovariectomy-induced increases and estradiol-induced decreased in body weight cannot be fully accounted for by changes in energy intake and appear to reflect alterations in thermogenesis. Because changes in energy expenditure have been linked to altered sympathetic nervous system (SNS) activity in brown adipose tissue (BAT), the role of estradiol in thermogenesis and body weight, as mediated by the SNS innervation of interscapular BAT (IBAT), was examined. The IBAT of ovariectomized rats was bilaterally or unilaterally surgically denervated. The chow-fed, bilaterally denervated group gained more weight than the unilaterally denervated or sham-operated group, an effect that was exaggerated by sucrose feeding. Food intake did not differ among the groups within each dietary condition. Estradiol benzoate (EB) injections decreased body weight in all groups. Bilateral, and to a lesser extent, unilateral IBAT denervation blocked the EB-induced increase in thermogenesis. Treatment with EB increased IBAT wet weight regardless of surgical treatment. Because IBAT denervation markedly decreased lipoprotein lipase activity and fatty acid synthesis/uptake, the estradiol-induced increase in denervated IBAT wet weight is most likely due to decreased lipolysis produced by the surgical sympathectomy. These results are discussed in terms of the role of the SNS and IBAT in the mediation of estradiol-induced changes in body weight and energy metabolism.

Effect of sucrose overfeeding on brown adipose tissue lipogenesis and lipoprotein lipase activity in rats.

During cold-induced nonshivering thermogenesis, interscapular brown adipose tissue (BAT) lipoprotein lipase (LPL) activity and lipogenesis are elevated. Because of the many similarities between cold- and diet-induced thermogenesis, we examined the effect of ad libitum access to a 32% sucrose solution on caloric intake, adiposity, and BAT enzyme activities in male rats. Daily caloric intakes of sucrose-fed animals were elevated by 20%-25%, and 8 wk of sucrose feeding doubled carcass fat content. This sucrose-feeding induced obesity was associated with increases in circulating triglyceride and insulin levels as well as increased retroperitoneal white adipose tissue LPL activity. However, the increased carcass lipid content accounted for less than half of the excess calories ingested by the sucrose-fed rats. Sucrose feeding stimulated in vivo lipogenesis in BAT and elevated BAT fatty acid synthetase and acetyl-CoA carboxylase activities but not LPL activity. These findings suggest that overeating enhances endogenous lipogenesis but not uptake of circulating triglyceride in BAT. Thus, both cold- and diet-induced thermogenesis increase BAT lipogenesis, while only cold-induced thermogenesis is associated with elevated LPL activity in BAT.

Lipectomy influences white adipose tissue lipoprotein lipase activity and plasma triglyceride levels in ground squirrels.

Golden-mantled ground squirrels undergo marked fattening and fat depletion during the prehibernatory and hibernatory phases, respectively, of their annual body weight cycle. Fat regulation was studied by surgical removal (lipectomy) of most of the inguinal-subcutaneous, retroperitoneal, and parametrial fat depots from female squirrels during the weight-gain phase of the annual cycle. Seven weeks after surgery, body weights of lipectomized (Lipx) and Sham-Lipx squirrels were equivalent, although white adipose tissue was not completely recovered in Lipx animals. Lipoprotein lipase (LPL) activity was markedly elevated in subcutaneous adipose tissue of Lipx squirrels, but not in other depots. Plasma triglyceride (TG) levels also were higher in Lipx squirrels 7 weeks after surgery. Changes in LPL activity and plasma TG may contribute to body mass and lipid restoration following lipectomy.

Effects of naltrexone and CCK on estrous behavior and food intake in Syrian hamsters.

Food deprivation inhibits estrous behavior in several species of rodents, but little is known about the neurotransmitter systems mediating this phenomenon. We determined whether partial blockade of opioid receptors by continuous infusion of naltrexone and/or acute peripheral injection of cholecystokinin (CCK) administration would overcome the suppressive effects of food deprivation on estrous behavior in Syrian hamsters. Contrary to expectation, naltrexone produced a slight suppression of estrous behavior, and systemic CCK administration had no effect. This dose of naltrexone was sufficient to reduce in vivo binding of [(3)H]naloxone in the brain, and both compounds affected other parameters such as food intake and body weight gain. Thus, the doses of CCK and naltrexone that were used were physiologically effective. These findings suggest that neither peripheral CCK nor opioid systems are likely to play a major role in the suppression of hamster estrous behavior by food deprivation.

Binding of [3-H]estradiol by brain cell nuclei and female rat sexual behavior: inhibition by antiestrogens.

The antiestrogens MER-25, CI-628, and nafoxidine inhibit the uptake of [3H]-estradiol in whole homogenates and isolated cell nuclei tissues and the pituitary, and inhibit estradiol-induced female sexual behavior. The antiestrogens were injected intraperitoneally 2 h prior to an intravenous injection of [3H]estradiol, and the animals were killed 2 h after the estradiol. CI-628 reduces radioactivity in whole homogenates and isolated cell nuclei of cerebral cortex, hypothalamus, preoptic area -septum and pituitary. Nafoxidine reduces uptake in cell nuclei of the hypothalamus, preoptic area-septum and pituitary. In this paradigm, MER-25 inhibited uptake only in the pituitary. In the analogous behavioral experiments, with antiestrogens injected 2 h prior to an intravenous injection of unesterified estradiol, CI-628 and nafoxidine totally inhibited lordosis responding. MER-25 shows no inhibition of behavior in this paradigm. However, when MER-25 is injected 12 h prior to the estradiol, it inhibits retention of [3H]estradiol at 2 h in brain and pituitary cell nuclei, and lordosis responding is also inhibited. Additionally, the antiestrogens can apparently displace previously bound [3H]estrdiol. When the antiestrogens are injected 2 h prior to an injection of [3H]estradiol, MER-25, CI-628 and nafoxidine all show greater inhibition of nuclear estradiol retention at 12 h after the [3H]estradiol injection than 2 h. Analogously, when CI-628 is injected 2 h after an intravenous injection of [3H]estradiol, it displaces most of the radioactivity present in hypothalamic-preoptic area nuclei at 12 h after the estradiol injection. These results indicate that antiestrogens can prevent or reverse the nuclear concentration of estradiol in brain cells and are consistent with a role of the cell nucleus in the induction of estrous behavior by estradiol.

PIP: In order to clarify the relationship between estradiol binding in the brain and its behavior actions, the effects of 3 antiestrogens (MER-25, CI-628, and nafoxidine) on in vivo tritiated estradiol uptake and retention in cell nuclear fractions or regions of the brain and pituitary were investigated. The ability of antiestrogens to block estradiol-induced female sexual behavior was also studied. Antiestroge were injected 2 hours prior to injection of tritiated estradiol and animals killed 2 hours later. Radioactivity in whole homogenates and isolated cell nuclei of cerebral cortex, hypothalamus, preoptic area-suptum, and pituitary was reduced by CI-628. Nafoxidine reduced uptake in cell nuclei of the hypothalamus, preoptic area-septum, and pituitary. MER-25 only inhibited uptake in the pituitary. CI-628 and nafoxidine totally inhibited lordosis while MER-25 was ineffective when injected 2 hours prior to testing. However, when MER-25 was injected 12 hours prior to testing it inhibited retention of tritiated estradiol in brain and pituitary cell nuclei and lordosis response. When antiestrogens were injected prior to estradiol injection all had greater inhibition of nuclear estradiol retention at 12 hours after the estradiol injection than at 2 hours. When CI-628 was injected 2 hours following injection of tritiated estradiol, most of the radioactivity present in the hypothalamic preoptic area nuclei at 12 hours after the estradiol injection was displaced. Thus antiestrogens can prevent or reverse the nuclear concentration of estradiol in the brain. Female sexual behavior seems to be induced by the presence of estradiol in the cell nucleus.

Uptake of (6,7-3H)estradiol-17beta in ovariectomized rats, guinea pigs, and hamsters: correlation with species differences in behavioral responsiveness to estradiol.

PIP: The amount of estradiol benzoate with progesterone required to induce lordosis in ovariectomized hamsters was determined to compare the responsiveness of hamsters to estradiol benzoate with that of rats and guinea pigs. In addition, the uptake and metabolism of tritiated estradiol in ovariectomized rats, guinea pigs, and hamsters was examined in an attempt to correlate species differences in behavioral sensitivity to estradiol with possible differences in neural affinity for the steroid. A dose of nearly 90 mg/kg was required to induce lordosis in 100% of the hamsters compared with the 2-5 mcg/kg which is effective in rats and guinea pigs. In all 3 species, highest uptake of estradiol was in the uterus and anterior pituitary gland. In the rat and guinea pig brains, the hypothalamus took up more estradiol than either the cortex or midbrain. In the hamster, there were no consistent differences in brain uptake. The affinity of the uterus, anterior pituitary, and hypothalamus of rats and guinea pigs for estradiol was greater than that of hamsters. In all 3 species, estrone was the principal metabolite of estradiol found in the tissues. The authors suggest that the higher the endogenous levels of a steroid, the less sensitive the animal is to that steroid.^ieng

Binding of [3H]estradiol by brain cell nuclei and female rat sexual behavior: inhibition by experimental diabetes.

In streptozotocin-diabetic female rats acute (24 h) withdrawal of insulin significantly impairs both estradiol + progesterone-induced sexual receptivity and cell nuclear concentration of [3H]estradiol in hypothalamus, preoptic area, and pituitary gland. Omission of insulin treatment for the first 24 h of a 30-h or 54-h estradiol benzoate-conditioning period significantly reduced mean lordosis ratings of ovariectomized-diabetic rats. Insulin withdrawal at the time of progesterone treatment and behavioral testing did not diminish sexual receptivity. One-half or 2 h after an intravenous injection of [3H]estradiol-17beta diabetic rats without insulin exhibited reduced cell nuclear [3H]estradiol concentrations (2 h) and/or diminished cell nuclear/whole homogenate concentration ratios (0.5 and 2 h). Twenty-four hour insulin withdrawal affected neither whole tissue [3H]estradiol uptake nor hypothalamus-preoptic area cytoplasmic estrogen-receptor content. These results: (1) suggest that diminished estradiol binding by target tissue cell nuclei may contribute to the well-known reproductive failures of female diabetics, and (2) support the concept that estradiol acts at the level of brain cell nuclei to induce female sexual behavior.

Estrogen-receptor immunoreactivity in hamster brain: preoptic area, hypothalamus and amygdala.

The distribution of estrogen-receptor containing cells in the preoptic area, hypothalamus and amygdala of female Syrian hamster brain was studied by immunocytochemical methods. Dense populations of estrogen-receptor immunoreactive (ER-IR) cells were found in the medial preoptic area, the bed nucleus of the stria terminalis, amygdala, ventral and lateral parts of the hypothalamus, and the arcuate nucleus. Injection of estradiol caused a decrease in estrogen-receptor immunoreactivity (ERIR) containing cells within one hour, a decrease that may reflect a change in the ability of the occupied estrogen receptor to bind the particular antibody (H222) used rather than down-regulation of the estrogen receptor. Our findings on the distribution of estrogen-receptor containing cells in these areas using an immunocytochemical technique are consistent with and extend the findings of others using autoradiographic and in vitro binding techniques to study estrogen receptor distribution in hamster brain.

Sexual dimorphism in brain weight of meadow voles: role of gonadal hormones.

In most adult mammals, brain weights of males exceed those of females. The role of androgens in the genesis of this sex difference was assessed in meadow voles by acute neonatal or chronic postweaning manipulation of testosterone titers. Female voles given a single injection of testosterone propionate (TP) on the second day of postnatal life had brain weights in adulthood that were indistinguishable from those of male voles and significantly heavier than those of control females. Whole brain DNA content, a measure of cell number, was not increased by neonatal TP treatment. Females treated with TP from day 19 to 70 had lower brain weights than control females and males gonadectomized at 19 days of age had greater brain weights than did intact male voles at day 70. The sex dimorphism in brain weight reflects organizational effects of testosterone during perinatal development. Beginning at weaning, and continuing through postpubertal development, testosterone decreases brain weight in both sexes. We suggest that testosterone affects brain weight by altering cell size or non-cellular components rather than cell number.

Long day lengths enhance myelination of midbrain and hindbrain regions of developing meadow voles.

Rates of brain growth differed in meadow voles maintained in long (LP) or short (SP) photoperiods postnatally. At 35 days of age, brain weight was greater by 6.6% in LP males and by 4.7% in LP females as compared to their SP counterparts. Whole brain galactolipid content, an index of brain myelin, was greater by 15.6% in LP as compared to SP males. At 70 days of age, brains of LP males were 4% heavier than those of SP males. Differences attributable to photoperiod were most pronounced in midbrain and hindbrain (8% and 14%, respectively). DNA and galactolipid contents were greater by 11% and 15%, respectively, in hindbrain of LP males. Photoperiod did not affect any of these measures in diencephalon, striatum, or cerebellum. Short day lengths reduce myelination in meadow voles, presumably by decreasing proliferation rates of oligodendroglia. This is one facet of a general delay in somatic development associated with being born at the end of the normal breeding season when day lengths are decreasing or below a critical threshold.

Long day lengths promote brain growth in meadow voles.

Male meadow voles kept in a long photoperiod (LP) from birth to 70 days of age have heavier brains than those kept in a short photoperiod (SP). Brain weights of male voles kept in the LP first exceeded those of SP animals at 20 days of age; differences were greatest at 35 days (5.8%) and persisted through 140 days of age (2%), although the magnitude of the difference declined progressively. Accelerated compensatory increases in brain weight were observed in voles transferred from the SP to the LP at 70 days of age. Total brain DNA content, an index of cell number, was not significantly affected by initial or final photoperiod, although it increased 7.8% within 70 days after voles were transferred from the SP to the LP. Brain weights (but not DNA content) of males exceeded those of females, but this sex difference was present only in the LP. We suggest that short day lengths retard brain development by reducing rates of myelination and possibly reducing cell size as well; this is part of a general retardation of somatic growth associated with a delayed onset of puberty that can be reversed by a stimulatory LP but, ordinarily, occurs spontaneously as voles become refractory to short day lengths.

Paraventricular nucleus lesions exaggerate dietary obesity but block photoperiod-induced weight gains and suspension of estrous cyclicity in Syrian hamsters.

Lesions of the paraventricular nucleus (PVN) of the hypothalamus block short photoperiod-induced testicular regression in Syrian hamsters. We examined the effects of PVN or sham lesions on the short photoperiod-induced increases in body weight and adiposity in female Syrian hamsters. PVN lesions did not affect body weight when hamsters were housed in a long photoperiod (LD, 16:8) and fed Purina laboratory rodent chow (No. 5001). However, when fed a high-fat diet both groups gained weight, and the hamsters with PVN lesions gained approximately twice as much as the sham-operated controls. When the hamsters were exposed to a short photoperiod (LD, 8:16), only the hamsters with sham lesions displayed the typical increase in body weight. No further increase in body weight or parametrial fat pad weight was seen when the hamsters with PVN lesions were exposed to the short photoperiod. The lack of a short photoperiod-induced increase in body weight gain in hamsters with PVN lesions seems unlikely to be due to a "ceiling effect" on body weight gain because we have routinely observed neurally intact, melatonin-treated female Syrian hamsters with body weight in excess of 250 g. Finally, the short photoperiod interrupted estrous cyclicity in sham-lesioned hamsters but not in those with PVN lesions. Thus, PVN lesions exaggerate dietary obesity but prevent short photoperiod-induced weight gains and vaginal acyclicity in female Syrian hamsters.