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PubMed1991

Sex differences in the development of learning abilities in primates.

The role of steroid gonadal hormones in promoting sex differences in reproductive behaviors has been thoroughly studied in numerous mammalian species. More recent experiments have indicated that the presence or absence of steroid hormones during the critical period of brain differentiation likewise might promote the development of sex differences in cognitive abilities. Studies in infant rhesus monkeys have demonstrated that there exist sex differences in learning abilities that can be altered by perinatal hormonal manipulations, suggesting that testosterone might be a crucial factor responsible for the development of sex differences in cognitive styles. In addition, neonatal lesion studies have shown that the cortical areas mediating specific learning abilities mature at different rates in male and female infant monkeys. These findings support the view that the perinatal hormonal environment can affect the rate of brain maturation by influencing neuronal connectivity at the cortical level. The combined data from sex differences in learning abilities in human infants and their reversibility in endocrinological syndromes suggest that testosterone may affect the maturation of the human brain in a manner similar to that demonstrated in nonhuman primates.

Animals↗
PubMed1994

Molecular aspects of sexual differentiation of the rodent brain.

The sexual differentiation of the brain is orchestrated by gonadal steroids during a restricted developmental period and results in permanent changes in the neural substrate including the capacity to support ovulation and expression of sex-specific reproductive behaviors. Sry gene-induced development of testes constitutes a binary switch directing all subsequent differentiation. Androgen produced by the testes of the embryonic male differentiates secondary sex characteristics but also acts in the brain to "masculinize" the neural substrate, many of the latter are the result of aromatization of testosterone to estrogen. Molecular characteristics of aromatase and 5 alpha-reductase enzymes are reviewed. It is assumed that estrogen binds to its receptor which then binds to DNA, inducing transcription of specific genes. Mutations in steroid receptor genes can markedly alter hormone-mediated differentiation. Two questions are addressed: (1), is the assumption correct that estrogen's effects on sexual differentiation are via the classic genomic action of steroids?; and (2) if so, what genes are transcribed as a result of the activated estrogen receptor complex? We have used antisense oligodeoxynucleotides designed to hybridize with and block the translation of mRNA for the estrogen receptor. Administration of antisense into brain of 3-day-old pups had permanent effects on estrogen-induced differentiation as indicated by behavioral and brain morphology differences in adulthood. These results demonstrate the effectiveness of antisense oligonucleotides if administered during a critical period and further confirm the widely accepted tenet that estrogen acts on the brain via its receptor. Subsequent experiments can now address the question of what genes are being activated by the estrogen receptor during development.

Animals↗
PubMed1994

Estrogen regulation of noradrenergic signaling in the hypothalamus.

Hypothalamic circuits utilizing the monoamine neurotransmitter norepinephrine (NE) may be key elements upon which the ovarian steroids estradiol (E2) and progesterone (P) act to regulate female reproductive behavior. Recent studies have focused on the modulation of hypothalamic NE release by E2 and P treatments that facilitate sexual behavior. Brain microdialysis studies suggest that oxytocin, a neuropeptide known to enhance lordosis when infused into the ventromedial hypothalamus (VMH) of E2 + P-primed females, modulates NE release in the VMH. Systemic administration of oxytocin reliably enhances extracellular NE levels in the VMH of animals primed with moderate doses of both E2 and P. Thus, ovarian steroids may facilitate female sexual behavior in part by promoting oxytocin-induced NE release in the VMH. Studies examining the release of 3H-NE from superfused hypothalamic slices indicate that estrogen treatment also facilitates NE neurotransmission by attenuating alpha 2-adrenergic receptor-mediated inhibition of NE release. Hypothalamic alpha 2-adrenergic receptors are not downregulated by estrogen, suggesting that brain adrenoceptor function can be modulated by E2 independent of changes in receptor density. A model is proposed wherein E2 and P enhance hypothalamic NE release, leading to increased excitability of VMH neuronal activity and the expression of lordosis behavior.

Animals↗
PubMedDate not supplied

Effects of ovarian hormones on levels of luteinizing hormone in plasma and on serotonin concentrations in discrete brain nuclei.

Levels of serotonin were measureed in microdissected, individual brain nuclei in ovariectomized rats after treatment with ovarian hormones. Regions sampled included nuclei in the forebrain, rostral and medial hypothalamus, and midbrain tegmentum. Estradiol benzoate decreased levels of luteinizing hormone in plasma but did not affect serotonin levels in any region. Progesterone alone elevated serotonin content in the nucleus tractus diagonalis and ventral tegmental area. The combined estrogen plus progesterone regime produced a surge in plasma luteinizing hormone and also markedly elevated serotonin in the median eminence. These results may be of significance for ovarian hormonal regulation of gonadotropin secretion and reproductive behavior.

Animals↗
PubMed1984

Electrographic recording from bovine vomeronasal capsule under spontaneous and stimulated conditions.

The vomeronasal organ ( VNO ) is an accessory olfactory system which in many vertebrates seems to be involved in reproductive behavior, particularly in permitting males to detect estrus in conspecific females. We postulated that EEG-like field potentials could be recorded from the VNO because the organ has a sensory epithelium that can discharge in response to odorants, and because VNO receptor cells are structurally similar to cells in the olfactory mucosa that produce field potentials (the "electro- olfactogram "). We examined this postulate in male cattle by surgically implanting recording/perfusion cannulae into the ducts leading to each VNO . Both bipolar (between VNOs ) and reference recording revealed continuous spontaneous voltage fluctuations that were similar to an EEG, except that amplitudes were larger and frequencies slower. Simultaneous recording of the EEG and VNO , using the same nasal reference electrode revealed that neither signal was "contaminated" by voltages from the other. Perfusions of one VNO with whole urine, urine condensate, or aqueous reconstituted urine extracts, whether from females in estrus or in anestrus, produced massive transient electrical responses from both VNOs . Perfusion with penicillin or local anesthetics caused more sustained large electrical responses from both VNOs , except that activity became quiescent about 15 min after local anesthesia. These results suggest that it is feasible to use direct recording of VNO responses to stimulation to investigate the behavioral physiology of the VNO .(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Evidence for reciprocal connections between the dorsochiasmatic area and the hypothalamo neurohypophyseal system and some related extrahypothalamic structures.

In the preceding article, a dorsochiasmatic area (DCh) was described that projects to both paraventricular (PVN) and supraoptic (SON) nuclei. The main afferents of the DCh, revealed by local injections of retrograde tracers, are the hypothalamic PVN and SON, lateral septal nuclei (LSV and SHy), bed nuclei of the stria terminalis (BST), anteroventral third ventricle region, particularly the median preoptic nucleus (MnPO), the subfornical organ, medial preoptic areas, arcuate hypothalamic nucleus, ventromedial hypothalamic nuclei, paraventricular thalamic nucleus, and, more caudally, several structures of the posterior hypothalamus and mesencephalon. The relations between DCh and BST, LSV, SHy, or MnPO appeared reciprocal. In view of their reciprocal relationships with the hypothalamo-neurohypophyseal system and some of their related extrahypothalamic structures, the DCh might be involved in the regulation of the vasopressin (AVP) and/or oxytocin (OT) systems, or in reproductive behavior.

Afferent Pathways↗
PubMed1981

Perinatal exposure to cannabichromene and delta 9-tetrahydrocannabinol: separate and combined effects on viability of pups and on male reproductive system at maturity.

The effects of cannabichromene (CBC), delta 9-tetrahydrocannabinol (delta 9-THC) and their combination (all doses 50 mg/kg orally) were determined after being administered to female mice for 7 days beginning on the 20th day of gestation. The THC treatment reduced postnatal viability, impaired male reproductive behavior at maturity and significantly reduced seminal vesicle weights. No changes from control values occurred after CBC or CBC + THC. Thus, CBC alone at this dosage did not act like THC; moreover, it antagonized the effects of THC when the two were given in combination.

Animals↗
PubMed1983

Age- and pregnancy-related changes in serum total cholesterol and triglyceride levels in the Cayo Santiago rhesus macaques.

Ninety-six free-ranging rhesus monkeys were evaluated for age-, sex-, and pregnancy-related changes in total serum cholesterol and triglyceride levels and compared with previous studies. Our findings indicate that pregnancy depresses total cholesterol in females and that cholesterol levels tend to increase in males with age. Triglycerides decreased significantly with advancing age in males. The Cayo Santiago monkeys represent a unique opportunity to study the effects of age on population of nearly 1200 nonhuman primates on which there is accurate data on birth date, lineage, behavior, reproduction and post-mortem morphology (skeletons). Further gerontological studies are necessary to take full advantage of this resource and to increase the presently-scant body of information on aging in monkeys for comparative studies on humans and for the development of animal models of gerontological diseases of humans.

Aging↗
PubMed1992

Hormonally-induced alterations in synaptic organization in the adult nervous system.

In recent years, there is growing evidence that vertebrate neural circuits involved in reproduction retain a considerable amount of plasticity in adulthood. Gonadal steroid hormones cause dramatic changes in the synaptic organization of these circuits to regulate the expression of reproductive behavior. Two model systems are described to illustrate such changes: the neural system controlling song in passerine birds, and the spinal nucleus of the bulbocavernosus system in the rat spinal cord.

Animals↗
PubMed1991

The effect of neonatal exposure to DES and o,p'-DDT on pituitary responsiveness to GnRH in adult castrated rats.

While exposure of vertebrates to estrogens during early development has been shown to alter adult reproductive behavior, neuroanatomy, and neurophysiology, effects on gonadotropin secretion have not been studied. We conducted the present studies to assess the effects of neonatal exposure to xenobiotic estrogens on luteinizing hormone secretion in castrated adult rats. Rat pups were injected with either corn oil, 1 micrograms diethylstilbestrol (DES), or 0.5 mg o,p'-DDT on postnatal days 1 to 10, and castration was performed on day 21. On day 42 of life, GnRH (50 ng/kg) was administered via right heart catheters, and blood was sampled for LH at 0, 5, 10, 15, and 30 min. Neonatal exposure to DES in both males and females significantly decreased basal and GnRH-induced LH secretion throughout the sampling period in castrated adults. o,p'-DDT significantly suppressed initial LH levels and blunted GnRH-induced release in males at the 5 min interval, while in females it had no effect. These data show that early exposure to environmental estrogens alters adult pituitary response to GnRH. Our results suggest that sexually distinct effects of environmental estrogens occur and can be readily demonstrated in this experimental model.

Animals↗
PubMed2004

Photoperiodic regulation of vasopressin receptor binding in female Syrian hamsters.

During long "summer-like" photoperiods, female Syrian hamsters display a regular 4-day estrous cycle. However, during short "winter-like" photoperiods (<12.5 h of light/day) hamsters become anestrus. Short photoperiod exposure eliminates reproductive behavior but social behaviors such as aggression and scent marking continue to be displayed. In long photoperiods, the types and intensity of social behaviors change as a function of the estrous cycle. For example, aggression and scent marking tend to occur at higher levels on diestrus 1 and diestrus 2 than on proestrus or estrus. Aggression and scent marking may be regulated, at least in part, by changes in the density of arginine vasopressin-V(1a) receptors (V(1a)R). In Experiment 1, it was hypothesized that the density of V(1a)R would change across the estrous cycle in several subcortical regions implicated in the regulation of aggression and scent marking. In Experiment 2, it was hypothesized that exposure to short photoperiod would alter the density of V(1a)R in several regions involved in the regulation of social behavior. Interestingly, there were no dramatic changes in V(1a)R binding across the estrous cycle within any of the neuroanatomical areas measured. However, in hamsters housed in short photoperiod, there were lower levels of V(1a)R binding within the medial preoptic nucleus (MPN), medial preoptic area (MPO), lateral hypothalamus (LH), central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis (BST) than in hamsters housed in long photoperiod. These data suggest that photoperiodic mechanisms can alter the density of V(1a)R in subset of V(1a) binding sites thought to be involved in the regulation of social behaviors in female hamsters.

Animals↗
PubMed2005

Gonadotropin-releasing hormone (GnRH) immunoreactive neurons in male mouse lemurs following removal of the vomeronasal organ.

Removal of the vomeronasal organ (VNO) in male mouse lemurs led to an increase in the number of immunoreactive gonadotropin-releasing hormone (GnRH) neurons in the medial preoptic area, compared to control males. No difference was found in the mediobasal hypothalamus. In this primate, which presents a fully functional VNO, the anterior part of the hypothalamus could be the major target for VNO-mediated regulation of GnRH function and the subsequent modulation of chemosensory dependent reproductive behavior.

Animals↗
PubMed2006

Cannabinoid system in the budgerigar brain.

Cannabinoid receptor density and cannabinoid receptor-mediated G protein stimulation were studied by autoradiographic techniques throughout the budgerigar (Melopsittacus undulatus) brain. The maximal CB(1) receptor density value (using [(3)H]CP55,940 as radioligand) was found in the molecular layer of the cerebellum (Mol), and high binding values were observed in the nucleus taeniae amygdalae (TnA), nucleus preopticus medialis, and nucleus pretectalis. The highest net-stimulated [(35)S]GTPgammaS binding values induced by the selective CB(1) receptor agonist WIN55,212-2 were observed in the nucleus paramedianus internus thalami, and high values of [(35)S]GTPgammaS binding were observed in the TnA, Mol, arcopallium dorsale and arcopallium intermedium. The distribution data suggest that in the budgerigar, as previously indicated in mammals, cannabinoid receptors may be related to the control of several brain functions in the motor system, memory, visual system, and reproductive behavior. The discrepancies between the cannabinoid receptor densities and the cannabinoid receptor-mediated stimulation found in several budgerigar brain nuclei support the hypothesis, previously described for mammals, of the existence of different G(i/o) protein populations able to associate with the cannabinoid receptors, depending on the brain structure, and could reflect the relative importance that cannabinoid transmission could exerts in each cerebral area.

Animals↗
PubMed2006

Vasopressin-induced translocation and proteolysis of protein kinase Calpha in an amphibian brain: modulation by corticosterone.

In urodele amphibians, the hypothalamic neuropeptide arginine vasotocin and the adrenal steroid corticosterone interact to regulate reproductive behavior by actions in the brain. The present study investigated signal transduction pathways underlying acute effects of vasotocin and corticosterone, presumably mediated via "non-genomic" steroid action, in an amphibian brain. We used Western blot to examine the effects of corticosterone and the vasotocin receptor agonist arginine vasopressin, alone and in combination, on the subcellular localization and proteolytic processing of protein kinase C-alpha (PKCalpha) in tiger salamander brain tissue. Treatment of whole brain minces with vasopressin or vasotocin led to increases in PKCalpha in membrane fractions and concurrent decreases in PKCalpha in cytosolic fractions. Vasopressin or vasotocin treatment also induced the appearance in membrane and cytosolic fractions of a PKCalpha-immunoreactive band that corresponds to PKMalpha, the proteolytically generated, free catalytic subunit of PKCalpha. Treatment with corticosterone alone had no consistent effect on either PKCalpha or PKMalpha in either fraction. However, pretreatment with corticosterone reliably blocked vasopressin-induced increases in cytosolic PKMalpha. These data provide new information about the cellular mechanisms of action of vasopressin and corticosterone in the vertebrate brain and suggest a cellular mechanism by which the two hormones interact to regulate neuronal physiology and behavior.

Ambystoma↗
PubMed2004

Decreased apoptosis in the forebrain of adult male medaka (Oryzias latipes) after aqueous exposure to ethinylestradiol.

Endocrine disrupting compounds (EDCs), especially those that are estrogenic, are an issue of growing concern because they may ultimately adversely affect wildlife survival. 17-beta-Estradiol and its synthetic counterpart, 17-alpha-ethinylestradiol, two common EDCs, are associated with intersex conditions and impaired male reproductive behavior in fish. Male and female Japanese medaka (Oryzias latipes) were exposed to 10 ng/l ethinylestradiol for 6 months. Using terminal dideoxynucleotidyl-mediated dUTP nick end-labeling (TUNEL) to quantitate cell death, we found that ethinylestradiol-exposed males had significantly fewer apoptotic cells in the forebrain compared to untreated males and exposed females. Our results show that the effects of ethinylestradiol exposure are highly variable among individuals of the same species and even within tissues of the same individual. Thus, when examining the effects of EDCs on natural populations, data from a variety of tissues should be examined and the interpretation of any effects should include consideration of tissue-specific processes.

Animals↗
PubMed2004

Critical peripartum disease in the mare.

The variety of diseases that occur in the peripartum mare require the examining veterinarian to evaluate the patient and the historical information carefullly so as to make an accurate diagnosis and begin appropriate therapy. An understanding of equine behavior, reproduction. mechanisms of shock,and gastrointestinal and reproductive physiology is requisite for accurate interpretation of the myriad of clinical signs of diseases present in this population. Attention to the unique metabolic and physiologic needs of the pregnant and lactating mare can aid the critical care clinician in providing optimum supportive care to enhance convalescence and improve outcome in the these critical patients.

Animals↗
PubMed2005

Review of outcomes of neonatal screening for cystic fibrosis versus non-screening in Europe.

We reviewed the published results of European prospective cohort and controlled studies and 1 randomized controlled study to assess whether newborn screening (NBS) for cystic fibrosis (CF) leads to an improved prognosis. We used long-term survival, early mortality, nutritional and pulmonary status, and the number of hospital admissions as outcome measures. Effects on reproductive behavior of the parents and relatives were also assessed. In 2 studies, a similar trend for improved long-term survival rate of the screened cohort was observed, whereas in 2 other studies CF NBS appeared to prevent CF-related deaths in infancy and early childhood. Screened patients born in the last 2 decades showed normal growth for height and weight from infancy until late childhood. In most studies, patients who were screened were found to have less lung damage than their non-screened peers. CF NBS significantly reduced the number of affected children who ever required hospitalization. In Brittany, France, a reduction of 15.7% in CF prevalence at birth was attributed to the introduction of a NBS program for CF. We conclude that there is accumulating evidence that CF NBS prevents early CF-related deaths and leads to a substantial and prolonged health gain for patients with CF.

Adolescent↗
PubMed2005

Analysis of spatiotemporal regulation of aromatase in the brain using transgenic mice.

Brain aromatase is widely distributed in the vertebrates, from fish to mammals, and plays important roles in functional reproductive behavior through production of estrogen as a neurosteroid. It is expressed only in the nerve cells of specific brain regions with a transient peak in the neonatal period when sexual behavior becomes organized, and therefore provides a good model system to study regulatory mechanism of cell-specific, brain region-specific, and developmental stage-specific expression. To elucidate spatiotemporal regulation of brain aromatase, we prepared transgenic mice carrying a reporter gene under the promoter of brain-specific exon 1f of the mouse aromatase gene. The reporter transgene carrying a 6.5 kb upstream region of the brain-specific promoter accurately reproduced the spatiotemporal expression patterns of aromatase in mouse brain, whereas transgenes carrying smaller fragments of the promoter showed ambiguous or inconsistent expression patterns. The binding sites of Aro-AI, Aro-AII, and Aro-B for nuclear factors were also identified in the proximal region of the exon 1f brain-specific promoter. Introduction of a mutation into the Aro-AII site in the reporter transgene carrying -6.5 kb promoter region of exon 1f caused complete alteration of the spatiotemporal expression pattern of the reporter gene in the transgenic mice. These results indicate that the -6.5 kb promoter region of exon 1f is the minimal essential element for brain-specific regulation, with both proximal and distal promoter regions required for accurate spatiotemporal expression of aromatase in the mouse brain.

Animals↗