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Endocrine events associated with spawning behavior in the sea lamprey (Petromyzon marinus).

Levels of estradiol, progesterone, and testosterone were determined in plasma of sea lamprey (Petromyzon marinus) undergoing certain behaviors associated with spawning in natural and artificial stream environments. Significantly higher levels of estradiol, progesterone, and testosterone were found in males than in females. In the artificial spawning channel, levels of estradiol were significantly higher in females exhibiting resting and swimming behaviors than in fanning, nest building, and spawning behaviors. No significant correlation was found with either progesterone or testosterone levels and the various reproductive behaviors. The data presented are the first experimental evidence that suggest gonadal steroids may be correlated with certain reproductive behaviors in the sea lamprey.

Aggression↗

Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice.

PRL is an anterior pituitary hormone that, along with GH and PLs, forms a family of hormones that probably resulted from the duplication of an ancestral gene. The PRLR is also a member of a larger family, known as the cytokine class-1 receptor superfamily, which currently has more than 20 different members. PRLRs or binding sites are widely distributed throughout the body. In fact, it is difficult to find a tissue that does not express any PRLR mRNA or protein. In agreement with this wide distribution of receptors is the fact that now more than 300 separate actions of PRL have been reported in various vertebrates, including effects on water and salt balance, growth and development, endocrinology and metabolism, brain and behavior, reproduction, and immune regulation and protection. Clearly, a large proportion of these actions are directly or indirectly associated with the process of reproduction, including many behavioral effects. PRL is also becoming well known as an important regulator of immune function. A number of disease states, including the growth of different forms of cancer as well as various autoimmune diseases, appear to be related to an overproduction of PRL, which may act in an endocrine, autocrine, or paracrine manner, or via an increased sensitivity to the hormone. The first step in the mechanism of action of PRL is the binding to a cell surface receptor. The ligand binds in a two-step process in which site 1 on PRL binds to one receptor molecule, after which a second receptor molecule binds to site 2 on the hormone, forming a homodimer consisting of one molecule of PRL and two molecules of receptor. The PRLR contains no intrinsic tyrosine kinase cytoplasmic domain but associates with a cytoplasmic tyrosine kinase, JAK2. Dimerization of the receptor induces tyrosine phosphorylation and activation of the JAK kinase followed by phosphorylation of the receptor. Other receptor-associated kinases of the Src family have also been shown to be activated by PRL. One major pathway of signaling involves phosphorylation of cytoplasmic State proteins, which themselves dimerize and translocate to nucleus and bind to specific promoter elements on PRL-responsive genes. In addition, the Ras/Raf/MAP kinase pathway is also activated by PRL and may be involved in the proliferative effects of the hormone. Finally, a number of other potential mediators have been identified, including IRS-1, PI-3 kinase, SHP-2, PLC gamma, PKC, and intracellular Ca2+. The technique of gene targeting in mice has been used to develop the first experimental model in which the effect of the complete absence of any lactogen or PRL-mediated effects can be studied. Heterozygous (+/-) females show almost complete failure to lactate after the first, but not subsequent, pregnancies. Homozygous (-/-) females are infertile due to multiple reproductive abnormalities, including ovulation of premeiotic oocytes, reduced fertilization of oocytes, reduced preimplantation oocyte development, lack of embryo implantation, and the absence of pseudopregnancy. Twenty per cent of the homozygous males showed delayed fertility. Other phenotypes, including effects on the immune system and bone, are currently being examined. It is clear that there are multiple actions associated with PRL. It will be important to correlate known effects with local production of PRL to differentiate classic endocrine from autocrine/paracrine effects. The fact that extrapituitary PRL can, under some circumstances, compensate for pituitary PRL raises the interesting possibility that there may be effects of PRL other than those originally observed in hypophysectomized rats. The PRLR knockout mouse model should be an interesting system by which to look for effects activated only by PRL or other lactogenic hormones. On the other hand, many of the effects reported in this review may be shared with other hormones, cytokines, or growth factors and thus will be more difficult to study. (ABSTRACT TRUNCATED)

Animals↗

Psychological factors affecting health after toxicological disasters.

Exposure to toxic substances in the environment is an ever more common event, that may cause physical as well as psychological harm. When an entire community is exposed, the term 'toxicological disaster' is used. The mere threat of such an event may be a source of stress, associated with changes in mental health, physical health, and changes in health-related behaviors. A review is presented of the literature about the effects of the stressful experience of toxicological disasters on health and health-related behaviors. Three questions are examined: (a) do toxicological disasters represent a specific type of stressor, different from other stressors?; (b) which stress-mediated health effects have been observed in the aftermath of toxicological disasters? and (c) is there evidence for a higher vulnerability in certain identifiable risk groups? On the basis of the available literature, it is concluded that toxicological disasters may have profound effects on subjective health, especially on symptom reporting, and on a number of psychophysiological parameters. Evidence for a substantial impact of disaster-related stress on either physical or psychiatric morbidity remains inconclusive. In this respect toxicological disasters do not appear to differ from other stressors. There is some evidence that toxicological disasters may have a more pronounced effect on health-related behaviors, especially on reproductive behavior (number of births and abortions). Women, and especially those who have young children to care for, appear to be more at risk for the observed health effects. The evidence for a higher vulnerability in other risk groups (e.g., former psychiatric patients remains inconclusive.

Adaptation, Psychological↗

The health of Navajo women: findings from the Navajo Health and Nutrition Survey, 1991-1992.

Cancer-screening behaviors, reproductive history, risk behaviors during pregnancy and chronic disease risk factors were examined in a representative sample of 566 Navajo women residing on the Navajo Reservation in 1991-1992. Among all women 15 y and older, 59% were overweight, 4% were current smokers, 10% currently used smokeless tobacco and 12% were anemic. Seventy-one percent of Navajo women aged 18 and older reported ever having had a Pap smear, but only 35% of women aged 50 and over reported ever having had a mammogram. Among parous women, the prevalence of having received no prenatal care for any pregnancy declined from 60% among women 60 and older to 13% among women 20-29 y of age, and the prevalence of ever having had a child born at home declined from 82 to 2%. These data suggest marked secular improvement in these pregnancy-related risk behaviors. However, data on cancer-screening behaviors indicate opportunities to improve health of Navajo women by increasing their use of mammography and Pap smear screening services.

Adolescent↗

Effect of transportation on sexual behavior of cats.

Transportation of an established feline colony approximately 1500 miles did not inhibit the resumption of behavioral reproductive cyclicity. Estrous behavior was observed as early as 18 days following shipment and mean duration of these first post-transfer estrous periods was normal. Relocation appeared to induce a synchronizing effect on behavioral cyclicity, since 76.2% and 42.9% of the population exhibited estrous onset during Days 18--31 and Days 24--26 respectively, following transport.

Animals↗

Oxytocin--a neuropeptide for affiliation: evidence from behavioral, receptor autoradiographic, and comparative studies.

Oxytocin (OT) is a nine amino acid peptide synthesized in hypothalamic cells which project either to the neurohypophysis or to sites within the central nervous system. Although neurohypophyseal OT release has long been associated with uterine contraction and milk ejection, the function of intracerebral OT remains unclear. On the basis of behavioral, cellular, and comparative studies, this review suggests that brain OT influences the formation of social bonds. The first part of this review examines evidence linking central OT to several forms of affiliation. Central administration of OT induces maternal and reproductive behaviors in rats primed with gonadal steroids. OT antagonists and hypothalamic lesions block the initiation of maternal and reproductive behaviors but have no effects on these behaviors once established. Our new studies in rat pups demonstrate that central OT selectively decreases the separation response, an effect which mimics social contact. These studies of parental, reproductive, and attachment behaviors suggest that exogenous OT has "prosocial" effects and that endogenous OT may be essential for initiating social interaction. In a second series of experiments, we investigated the cellular mechanisms for OT's effects on social behavior by means of autoradiographic receptor binding. In the rat forebrain, OT receptors are expressed in several limbic regions believed to be involved in the integration of sensory processing. The regulation of these receptors is surprisingly resistant to either ablation of OT cells or repeated central administration of OT. However, receptors in two regions, the bed nucleus of the stria terminalis (BNST) and the ventromedial nucleus of the hypothalamus (VMN), appear selectively induced by exogenous or endogenous increases in gonadal steroids. At parturition, binding to OT receptors increases 84% in the BNST, and at estrus, binding increases 35% in the VMN. These results demonstrate that physiologic changes in gonadal steroids can alter receptor expression in anatomically discrete target fields and thereby direct responsiveness to endogenous neuropeptide release. A model for OT's effects on social behavior is proposed, which relies on the heterologous regulation of the brain OT receptor. A third series of experiments tested the hypothesis that brain OT influences affiliation by comparing prairie and montane voles, two closely related species with dichotomous systems of social organization. Although no differences appear in the presynaptic expression of the neuropeptide, OT receptors are distributed in complementary patterns in the two species. In the highly affiliative prairie vole, receptors are most evident in the BNST and one of its primary afferents, the lateral amygdala, highlighting a circuit previously implicated in maternal behavior.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The effect of diabetes on sexual behavior and reproductive tract function in male rats.

The effect of streptozotocin induced diabetes and sabeluzole (SBZ) on sexual function was evaluated in male rats. SBZ is a benzothiazole derivative with antihypoxic and antiischaemic activities. Rats were rendered diabetic by intraperitoneal injection of streptozotocin, 60 mg./kg. body weight, and either left untreated or treated with 1.0 mg./kg. of SBZ. Two groups of control rats treated with or without SBZ were also evaluated. Seven weeks after the induction of diabetes, all rats were studied in vivo for mating behavior. Animals were sacrificed one week later, and detrusor strip response in vitro was evaluated. The reproductive organ weight, sperm content and motility as well as in vitro testosterone secretion and serum levels of LH and testosterone were determined. Diabetes induced significant reduction in mating behavior. The diabetic rats that received SBZ showed a significant improvement in mating behavior. The percentage of animals that exhibited ejaculation was 0% in the diabetic group compared to 70% in the controls and 38% in diabetic plus SBZ group. The strips of the detrusor muscle of the diabetic group showed a marked hypersensitivity to bethanechol HCL. In the diabetic plus SBZ group, the strips of the detrusor muscle showed a response similar to that of the control. The diabetic rats had significantly diminished reproductive organ weight, testicular sperm content, epididymal sperm content and sperm motility relative to the control. In addition, marked decrease in the serum level of testosterone and in vitro testosterone secretion was observed in diabetic rats. In the diabetic plus SBZ group, the reproductive organ weight, sperm content and motility as well as serum testosterone and in vitro testosterone secretion showed an improvement compared to diabetic rats. In summary, our data suggest that sex behavior and reproductive tract functions are markedly affected by streptozotocin induced diabetes. Sabeluzole treatment could be beneficial in reducing the deleterious effect of diabetes on sexual functions.

Animals↗

Sex differences in the vomeronasal system.

In the early eighties we found sex differences in the vomeronasal organ (VNO) and hypothesized that the vomeronasal system (VNS), a complex neural network involved in the control of reproductive behavior, might be sexually dimorphic. At that time sex differences had already been described for some structures that receive VNO input, such as the medial amygdala, the medial preoptic area, the ventromedial hypothalamic nucleus, and the ventral region of the premammillary nucleus. Since then, we have shown sex differences in the accessory olfactory bulb (AOB), the bed nucleus of the accessory olfactory tract (BAOT), and the bed nucleus of the stria terminalis (BST). When new VNS connections were found, all of them ended in nuclei that present sex differences. In general, sex differences in the olfactory system show two morphological patterns: one in which males present greater morphological measures than females, and just the opposite. To explain the morphometric measures of males in the latter, it has been hypothesized that androgens serve as inhibitors. Our work on the involvement of the GABA(A) receptor in the development of AOB and maternal behavior sex differences also suggests that neonatal changes in neuronal membrane permeability to the ion Cl- differences. This might be the first animal model to help us to understand the situation in which human genetic and gonadal sex do not agree with brain and behavioral sex. Finally, we stress that sex differences in the VNS constitute a neurofunctional model for understanding sex differences in reproductive behaviors.

Animals↗

Interactions between behavior and plasma steroids within the scramble mating system of the promiscuous green turtle, Chelonia mydas.

We measured plasma androgen (combined testosterone and 5alpha-dihydrotestosterone) (A) and corticosterone (B) in the promiscuous green turtle (Chelonia mydas) during courtship in the southern Great Barrier Reef. This study examined if reproductive behaviors and intermale aggression induced behavioral androgen and adrenocortical responses in reproductively active male and female green turtles. Associations between reproductive behavior and plasma steroids were investigated in green turtles across the population and within individuals. Levels across a range of both asocial and social behaviors were compared including (a) free swimming behavior; (b) initial courtship interactions; (c) mounted behavior (male and female turtles involved in copulatory activities); (d) intermale aggression (rival males that physically competed with another male turtle or mounted males recipient to these aggressive interactions); and (e) extensive courtship damage (male turtles that had accumulated excessive courtship damage from rival males). Behavioral androgen responses were detected in male turtles, in that plasma A was observed to increase with both attendant and mounted behavior. Male turtles who had been subjected to intermale aggression or who had accumulated severe courtship damage exhibited significantly lower plasma A than their respective controls. No pronounced adrenocortical response was observed after either intermale aggression or accumulation of extensive courtship damage. Female turtles exhibited a significant increase in plasma B during swimming versus mounted behavior, but no change in plasma A. We discuss our results in terms of how scramble polygamy might influence behavioral androgen interactions differently from more typical combative and territorial forms of male polygamy.

Aggression↗

A concept of physiological time: rhythms in behavior and reproductive physiology.

Biological clocks are self-sustained and endogenous. Animals have biological clocks in a variety of frequencies. Biological clocks provide temporal coordination among physiological, behavioral, and environmental events. One important function of steroid hormones may be to alter the temporal coordination among those events. Biological clocks provide a referent mechanism for the timing of both current and future endogenous and exogenous events. Physiological time is a unifying principle in biology.

Animals↗

Differential regulation of proenkephalin gene expression by estrogen in the ventromedial hypothalamus of male and female rats: implications for the molecular basis of a sexually differentiated behavior.

The ventrolateral aspect of the ventromedial hypothalamic nucleus (VL-VM) contains many estrogen-concentrating neurons which mediate estrogen facilitation of reproductive behavior. Previous studies have shown that estrogen treatment increases proenkephalin (PE) gene expression in neurons of the VL-VM in ovariectomized female rats, and that enkephalin peptides may stimulate lordosis behavior. To determine whether there is a sex difference in steroid hormone regulation of PE gene expression we have examined the effects of estrogen and testosterone on PE mRNA levels in male rats. Slot blot hybridization analysis of RNA isolated from the ventromedial hypothalamus indicated that estrogen treatment increased PE mRNA levels in the VL-VM of ovariectomized female rats (2.2-fold), but had no measurable effect on PE mRNA levels in gonadectomized males. Testosterone treatment of gonadectomized males also had no effect on PE gene expression. To determine whether the sex difference in estrogen-inducibility of PE gene expression is due to the developmental effects of gonadal steroids, we have investigated the effect of estrogen on PE mRNA levels in the VL-VM of neonatally androgenized female rats. Unlike the genetic male, the androgenized females responded to estrogen treatment with a female-typical increase in PE mRNA levels (1.7-fold). Further, although the androgenized rats clearly exhibited signs of defeminization, they did exhibit estrogen-facilitated lordosis behavior when tested with manual stimulation. The PE mRNA induction in estrogen-treated androgenized rats correlated well with the lordosis scores obtained by manual stimulation testing. These results indicate that estrogen regulation of PE gene expression in the VL-VM is sexually differentiated and support the hypothesis that the enkephalinergic neurons of the VL-VM are involved in the regulation of female reproductive behavior.

Animals↗

Behavioral and reproductive effects of chronic developmental exposure to brominated vegetable oil in rats.

Adult Sprague-Dawley rats were fed diets containing 0, 0.25, 0.5, 1.0, or 2.0% of the food additive brominated vegetable (soybean) oil (BVO) for 2 weeks prior to mating. After conception, the diets were continued throughout gestation and lactation for the females. The same diets were also provided to the dams' offspring throughout their development (up to 90-120 days of age). BVO at 2.0% of the diet completely blocked reproduction. BVO at 1.0% of the diet severely impaired conception, reduced maternal body weight, and produced slightly reduced litter sizes but no evidence of malformations. At this dose postnatal mortality was high, and survivors showed impaired growth and severe behavioral impairments on a battery of standardized tests of functional development. After weaning, adequate data could not be obtained because of the high mortality rate in this group. BVO at 0.5% of the diet produced less reproductive interference and much less offspring mortality or impairment of growth, but produced behavioral impairments almost as severe as seen in the BVO 1.0% group. In addition, this group exhibited severely reduced postweaning activity, delayed vaginal patency development, and reduced day-90 weight. BVO at 0.25% of the diet produced reproductive deficits similar to the BVO 0.5% group, but less severe effects on growth and behavioral development. This group showed no significant increase in offspring mortality. The data demonstrate clear evidence of dose-related physical and behavioral developmental toxicity.

Animals↗

[Results of a case-control study of the current effect of various factors on risk of cervix cancer. 1. Factors in reproduction, sex behavior and infectious genital diseases].

We performed a case control study to determine factors which influence the development of cervical carcinoma. Factors like reproduction, sexual behaviour and genital infections were considered. 309 patients with cervical intraepithelial neoplasia (CIN) or invasive cervical carcinoma were interviewed as a study group. 490 patients with no cervical changes served as control group. The two groups of patients had a different age distribution with an early age summit in the study group. No differences were observed in relation to residence areas and attendance of screening for cervical carcinoma. 83.5% of the women in the study group (n = 258) and 81.0% (n = 397) of the control group attended the screening for cervical carcinoma. According to our observation, the following factors increased the risk of CIN or invasive cervical carcinoma: early menarche (< 14 years vs > 14 years), multiparity (0 vs 1-3 vs > 4), first pregnancy before the age of 20, divorced women, early sexual contact (< 14-17 years vs 18-21 years vs > 21 years), multiple sexual partners, vaginal discharge and venereal diseases (gonorrhea, syphilis). Factors like reproductive characteristics and genital infections can be interpreted as expressions of sexual behaviour. Despite the improving social status, increasing health consciousness and extensive mass-screening for cervical cancer, the above mentioned risk factors still play an important role. Risk group should be followed and examined strictly so as to reduce the rate of invasive cervical carcinoma in screened patients.

Adolescent↗

Progesterone modulation of androgen receptors in the brain and pituitary of male guinea pigs.

Androgen receptors (AR) were determined in cytosol and nuclear extracts of pituitary and neural tissue from intact male guinea pigs by a binding assay using [3H]dihydrotestosterone as ligand. Saturation analyses of cytosol from hypothalamus-preoptic area (POA)-amygdala regions and anterior pituitary revealed receptors (ARc) with apparent Kd values of 2.52 and 3.83 X 10(-10) M, respectively. Nuclear salt extracts from the same tissues contained receptors (ARn) with Kd values of 4.38 and 5.12 X 10(-10) M. Reproductive behavior of 10 males was observed with receptive females for 10 min once a week. After 4 weeks, half of the animals received 10 mg progesterone (P)/day for an additional 4 weeks. P treatment significantly (P less than 0.05) increased latency to first mount and decreased mounts per test period. After behavioral testing, analysis of the AR content of specific brain regions revealed that the highest concentrations of ARc and ARn were in the POA and medial basal hypothalamus, and the lowest were in the cerebral cortex. The ARn content was significantly suppressed in POA and medial basal hypothalamus (P less than 0.05) from P-treated males compared to the control value. These data show that AR content is highest in areas thought to control behavior and gonadotropin release within the brain of the male guinea pig. In addition, the antiandrogenic actions of P on the central nervous system, which in this experiment were expressed as a significant decline in reproductive behavior, may be explained by its interference with the retention of the AR in the nucleus.

Amygdala↗

Dopaminergic regulation of progesterone receptors: brain D5 dopamine receptors mediate induction of lordosis by D1-like agonists in rats.

To characterize the signaling pathway by which the neurotransmitter dopamine modulates progesterone receptor (PR) activation, the steroid-dependent behavior lordosis was used in estrogen-primed ovariectomized Sprague-Dawley rats with stereotaxic implanted third ventricle cannulas. Lordosis was observed in response to solicitous males in females after central administration of the D1-like agonist SKF38393 and three of its analogs (SKF77434, SKF75640, and SKF85174). In contrast, D1-like antagonist SCH23390 and D1-like/D2 repopulation inhibitor EEDQ blocked behavior inducible by the D1-like agonists. Further, antisense oligonucleotides to D5, but not D1, dopamine receptor mRNA suppressed reproductive behavior associated with D1-like stimulation. This finding provides strong evidence that dopaminergic modulation of lordosis is mediated by the novel D5 dopamine receptor. Although D1, but not D5, dopamine receptor mRNAs were detected in the ventromedial nucleus (VMN) by in situ hybridization, agonists microinjected into the VMN, but not into the arcuate nucleus or preoptic area, induced lordosis, suggesting the functional presence of D5 dopamine receptors in the VMN. Also in support, D5 receptor mRNA antisense microinjected into the VMN blocked the subsequent induction of lordosis by D1-like agonists. Finally, facilitation of sex behavior by D1-like agonists was blocked by the antiprogestin RU38486 and PR antisense oligonucleotide. Collectively, the data provide strong evidence for dopaminergic modulation of reproductive behavior through D5 dopamine receptor-mediated modulation of PR-dependent behavior in rat CNS.

Animals↗

Effects of apomorphine on sexual behavior in male quail.

In the rat, dopamine (DA) facilitates male copulatory behavior. Indirect evidence based largely on neuroanatomical data suggest that in quail DA is also implicated in the control of male reproductive behavior but there is no pharmacological evidence to support this conclusion. To test this idea, castrated testosterone (T)-treated male quail were injected with various doses of the dopaminergic agonist apomorphine (APO) in the range 1-10,000 micrograms/kg. The sexual behavior of birds was recorded starting 15 min after APO injection for a duration of 30 min. A dose-dependent inhibition of male reproductive behavior that lasted for the entire duration of the test was observed. In a second experiment, gonadectomized T-treated male Japanese quail were injected daily with APO (0, 10, or 1,000 micrograms/kg) during 8 days. Their sexual interactions with a partner were quantified either 24 h or 15 min after the last injection. No influence of the treatment on copulatory behavior was observed 24 h after the last injection, but a strong inhibition was present when the test was performed 15 min after. To research whether the inhibitory effects of APO were due to a preferential action on D2 presynaptic autoreceptors, male quail were pretreated with two different D2 antagonists (spiperone or pimozide; 0.5 or 2 mg/kg) before being injected with APO (100 micrograms or 1 mg/kg). Spiperone facilitated male sexual behavior but did not suppress the inhibitory effect of APO. No significant effect of pimozide was observed. These results support the notion that DA modulates male sexual activity in the Japanese quail. The specific role of the different dopaminergic receptor subtypes remains, however, to be elucidated.

Animals↗