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PubMed1992

Development of the limbic-hypothalamic cholecystokinin circuit: a model of sexual differentiation.

Reproductive behavior is the final outcome of the integration of appropriate gonadal hormonal stimulation with olfactory and somatic cues by the steroid-sensitive limbic-hypothalamic neural circuit. Gonadal hormones sexually differentiate the structure and neurochemistry of this circuit during development. In adulthood, gonadal steroids continue to regulate the behavioral response of the animal through their effects on intercellular signalling in this limbic-hypothalamic circuit. Recently, the neuropeptide cholecystokinin has been demonstrated to be an important intercellular messenger, expression, distribution, levels, and receptors of which are regulated both during development and adulthood by the gonadal steroid environment. Studies on the development of sex differences using the cholecystokinin component of this circuit as a model have yielded insight into how gonadal steroids modulate the neurochemistry of the reproductively relevant limbic-hypothalamic circuit. Concentrating on this circuit and its role in reproduction, we will review the data about gonadal steroid effects on the distribution, expression, development, and physiology of cholecystokinin and its receptors.

Amino Acid Sequence↗
PubMed1992

Male sexual signaling is defective in mutants of the apterous gene of Drosophila melanogaster.

The apterous (ap) gene of Drosophila melanogaster exhibits extreme pleiotrophy: its functioning is essential for life, normal wing structure, juvenile hormone production, female fertility, and normal development of female sexual receptivity. Four mutant ap alleles (ap4, ap56f, apc, and apblt) were characterized for three additional phenotypes: male mating success, courtship behavior, and immature male sex appeal (the ability of males to stimulate homosexual courtship). Mating success with mature wild-type virgin females is reduced in males mutant for the ap gene, the extreme case being ap4/ap4 males, which are behaviorally sterile. In ap mutants, nonwing courtship elements are qualitatively like those of ap+/ap+ males. However, the mean rate of nonwing courtship directed toward virgin wild-type females (i.e., the mean temporal frequency of these displays) is reduced in males homozygous for ap4, ap56f, or apc alleles. In contrast, the apblt allele makes for wild-type rates of nonwing courtship. Immature male sex appeal persists for at least 3 days in males homozygous for apc and, to a lesser extent, in ap56f or ap4 homozygotes; apblt/apblt and wild-type males lose immature male sex appeal after 1 day. All three male phenotypes map to the ap locus, which is therefore essential for the development of normal levels of male courtship and male mating success and for the timely loss of immature male sex appeal. For each phenotype, ap+ is dominant to ap alleles making for behavioral abnormalities, with a single exception (for rate of nonwing courtship, ap+/apc was low). For mating success and frequency of nonwing courtship, each allele pair exhibits at least partial complementation, except for ap4 and ap56f, which fail to complement. For immature male sex appeal, apc, ap4, and ap56f fall into the same complementation group. Juvenile hormone production is not correlated with effects on male reproductive behavior.

Animals↗
PubMed1991

A corticosteroid receptor in neuronal membranes.

Steroids may rapidly alter neuronal function and behavior through poorly characterized, direct actions on neuronal membranes. The membrane-bound receptors mediating these behavioral responses have not been identified. [3H]Corticosterone labels a population of specific, high-affinity recognition sites (dissociation constant = 0.51 nanomolar) in synaptic membranes from an amphibian brain. These binding sites were localized by receptor autoradiography in the neuropil, outside the regions of perikarya. The affinities of corticoids for this [3H]corticosterone binding site were linearly related to their potencies in rapidly suppressing male reproductive behavior. Thus, it appears that brain membranes contain a corticosteroid receptor that could participate in the regulation of behavior.

Amphibians↗
PubMedDate not supplied

The potential impact of changes in fertility on infant, child, and maternal mortality.

In this paper we explore the relation between changes in reproductive behavior, such as those that might result from an effective family planning program in developing countries, and changes in child and maternal mortality. Specifically, we use the results from recent multivariate studies to estimate the changes in mortality that might result from altering maternal age, birth order, and birth spacing distributions of live births. Our results indicate that if childbearing were confined to the "prime" reproductive ages of 20-34, then infant and child mortality rates would fall by about 5 percent. Limiting childbearing to ages 20-39 may also reduce the maternal mortality ratio by 11 percent. The elimination of fourth and higher order births would reduce the maternal mortality ratio by about 4 percent. Universal adoption of an "ideal" spacing pattern in which all births subsequent to the first are spaced at least two years apart may reduce infant mortality by about 10 percent and child mortality by about 21 percent.

Birth Intervals↗
PubMed2006

Comparative endocrine investigations in three bear species based on urinary steroid metabolites and volatiles.

In order to improve breeding of in situ populations of bears, a comprehensive study of reproductive physiology in Brown (Ursus arctos), Spectacled (Tremarctos ornatus) and Giant panda bears (Ailuropoda melanoleuca) was performed. The objective was to perform non-invasive analyses of urinary and fecal steroid metabolites. In addition, we investigated the presence of reproduction-related urinary volatile substances of these bears that might trigger the reproductive behavior. Urinary estrogen concentrations, routinely used to monitor follicular activity in Giant panda, were inappropriate for monitoring follicular activity in Spectacled bear. In addition, no estrogen peak related to mating activity was observed in Brown bear. Further contrasting Giant panda, although urinary pregnanediol analyses failed to indicate luteal activity in either Spectacled or Brown bears, urinary (Spectacled bear) and fecal (Brown bear) concentrations of progesterone were an appropriate indicator of luteal activity. The Giant panda had volatile components (medium-chain fatty acids) in their urine that increased simultaneously with the seasonal increase of estrogens. These fatty acids were also detected in the Brown during estrus and Spectacled bear. Further studies on the behavioral relevance of these fatty acids are required to determine if they are pheromones.

Androsterone↗
PubMed1995

The nuclear receptor steroidogenic factor 1 is essential for the formation of the ventromedial hypothalamic nucleus.

The nuclear receptor steroidogenic factor 1 (SF-1) regulates the biosynthesis of the two essential mediators of male sexual differentiation, androgens and Müllerian-inhibiting substance, and is required for adrenal and gonadal development and gonadotropin expression. SF-1 is also expressed in the embryonic ventral diencephalon, subsequently localizing to the ventromedial hypothalamic nucleus, a region important for reproductive behavior. Mice lacking SF-1 secondary to targeted disruption of the Ftz-F1 gene had normal numbers and location of GnRH neurons but exhibited grossly impaired ventromedial hypothalamic nucleus structure. Despite their apparently normal GnRH neurons, treatment of Ftz-F1-disrupted mice with GnRH restored pituitary gonadotropin expression. These studies define SF-1's essential role within a discrete hypothalamic nucleus previously linked to reproduction.

Animals↗
PubMed2005

Inhibition of steroid receptor coactivator-1 blocks estrogen and androgen action on male sex behavior and associated brain plasticity.

Studies of eukaryotic gene expression demonstrate the importance of nuclear steroid receptor coactivators in mediating efficient gene transcription. However, little is known about the physiological role of these coactivators in vivo. In Japanese quail, the steroid receptor coactivator-1 (SRC-1) is broadly expressed in steroid-sensitive brain areas that control the expression of male copulatory behavior, and we investigated the role of this coactivator by antisense technology. Daily intracerebroventricular injections of locked nucleic acid (LNA) antisense (AS) oligonucleotides targeting SRC-1 significantly reduced the expression of androgen- and estrogen-dependent male-typical sexual behaviors compared with control animals that received the vehicle alone or scrambled oligonucleotides. Sexual behavior was restored and even enhanced within 48 h after interruption of LNA injections. Western blot analysis confirmed the decrease of SRC-1 expression in AS animals and suggested an overexpression 48 h after the end of injections. The effects of SRC-1 knock-down on behavior correlated with a reduction in volume of the preoptic medial nucleus (POM) when its borders were defined by Nissl staining or by aromatase immunohistochemistry. The amount of aromatase-immunoreactive material in POM was also reduced in the AS compared with the control group. Previous work on SRC-1 knock-out mice raised questions about the importance of this specific coactivator in the regulation of reproductive behavior and development of sexually dimorphic structures in the CNS. Together, the present findings indicate that SRC-1 modulates steroid-dependent gene transcription and behavior and highlight the rapid time course of steroid-induced brain plasticity in adult quail.

Androgen Antagonists↗
PubMed2002

Androgen and behavior in the male three-spined stickleback, Gasterosteus aculeatus. II. Castration and 11-ketoandrostenedione effects on courtship and parental care during the nesting cycle.

Courtship declines and ceases while parental care increases in the presence of developing eggs during the nesting cycle of the male three-spined stickleback, Gasterosteus aculeatus. Furthermore, circulating 11-ketotestosterone (11KT) levels are higher during the initial "courtship phase" than during the later "parental phase," similar to that found in other paternal fishes. This study aimed to investigate a possible functional relationship between changes in 11KT levels and changes in reproductive behavior during the nesting cycle. To this end, groups of nonspawned and spawned male sticklebacks were sham-operated, castrated, or castrated and treated with 11-ketoandrostenedione (11KA), and the effects of the treatments on courtship and parental care were studied. Castration removed circulating 11KT, while 11KA replacement prevented the natural decline in 11KT during the parental phase (11KA converts to 11KT extratesticularly), as assessed by radioimmunoassay. Regardless of treatment, parental care remained low and courtship was present in all nonspawned males, even at the end of the experiment. However, courtship did eventually decline in castrated nonspawned males compared to the other two nonspawned groups. In all treatments of spawned males there was a drastic decline in courtship and an increase in parental care. In castrated spawned males, however, the decline in courtship came earlier than in the other two spawned groups. 11KA treatment did not prevent the natural decline in courtship/increase in parental care in spawned males, indicating that the natural decline in 11KT is not responsible for the main portion of the rapid changes in these behaviors over the stickleback's nesting cycle. The limited effects of castration also exclude other gonadal hormones from being responsible for most of these changes.

Androgens↗
PubMed1988

Effects of male social status on reproductive success and on behavior in mice (Mus musculus).

Differences in reproduction as well as in behavior in the presence of females were evaluated according to dominant and subordinate male rank in albino mice, in the temporary absence of each male's antagonist. Dominant males reproduced more successfully than subordinate males. Subordinate males were generally inactive, except for displacement activities, during the first 15 min they were exposed to female partners. These findings suggest that mechanisms other than male-male interference or mating order may be operating or influencing behavior and reproductive results.

Agonistic Behavior↗
PubMed2002

Noradrenergic control of auditory information processing in female canaries.

An ethological procedure, based on the study of the sexual responsiveness of female canaries (Serinus canaria) to song playbacks was used to investigate the function of central noradrenergic inputs in the processing of auditory information. The effects of a noradrenergic denervation on sexual responses was analyzed in females exposed to playbacks of biological relevant auditory stimuli, i.e. sexually stimulating songs, presented alone or masked by auditory distractors. A decrease in behavioral responsiveness was observed as a function of the amount of masking distractors indicating that female canaries have the perceptual ability to discriminate and selectively attend to biologically relevant songs. After the systemic administration of DSP-4, a specific noradrenergic neurotoxin, females exhibited an overall decrease in sexual responsiveness to songs masked or not by distractors. No effect of DSP-4 were detected on the motor activity nor on reproductive behaviors. These results indicate that central noradrenergic inputs modulate the sexual behavior of female canaries by affecting the auditory processing of relevant information contained in sexually stimulating songs.

Acoustic Stimulation↗
PubMed1994

Sexually transmitted diseases and other risk factors for cervical dysplasia among southwestern Hispanic and non-Hispanic white women.

OBJECTIVE: To assess risk factors for high-grade cervical dysplasia among southwestern Hispanic and non-Hispanic white women. DESIGN: Clinic-based case-control study. SETTING: University-affiliated gynecology clinics. SUBJECTS: Cases were Hispanic and non-Hispanic white women with biopsy-proven high-grade cervical dysplasia (n = 201). Controls were Hispanic and non-Hispanic white women from the same clinics with normal cervical epithelium (n = 337). METHODS: Study design included interviews focused on histories of sexually transmitted diseases, sexual behavior, reproductive histories, hygienic practices, contraceptive use, cigarette smoking, and diet. Laboratory studies included bacterial and protozoal cultures of the cervix; hybridization tests to identify human papillomavirus (HPV) genome with commercial (ViraPap and ViraType) and polymerase chain reaction-based assays; and serum antibody tests for herpes simplex virus, Chlamydia trachomatis, syphilis, hepatitis B, and hepatitis C. RESULTS: For both ethnic groups combined, after adjustment for ethnicity, age, and sexual behavior, the strongest risks for cervical dysplasia were associated with cervical HPV infection as identified by ViraPap (odds ratio [OR], 12.8; 95% confidence interval [CI], 8.2 to 20.0) or with polymerase chain reaction (OR, 20.8; 95% CI, 10.8 to 40.2). Other factors associated with dysplasia included cigarette smoking at the time of diagnosis (OR, 1.8; 95% CI, 1.2 to 2.8); low income (OR, 2.2; 95% CI, 1.2 to 4.0); low educational level (OR, 6.2; 95% CI, 3.4 to 11.1); history of any sexually transmitted disease (OR, 1.9; 95% CI, 1.3 to 2.7); and seroprevalence of antibodies to hepatitis B (OR, 1.8; 95% CI, 0.9 to 3.5). For Hispanic women, HPV 16/18 identified by ViraType was strongly associated with cervical dysplasia (OR, 171.0; 95% CI, 22.8 to 1280.5). Antibodies to herpes simplex virus type 2 were not associated with dysplasia in Hispanic women but were significantly associated with dysplasia among non-Hispanic whites. Risks associated with cigarette smoking also varied by ethnic group. CONCLUSIONS: The strongest risk factor associated with high-grade cervical dysplasia among clinic attendees was HPV infection. Although most of the risk factors we examined showed similar associations for dysplasia for both ethnic groups, our data suggest that several different risk factors may be relevant to the development of cervical dysplasia in Hispanics compared with non-Hispanic whites who attend the same clinics.

Adolescent↗
PubMed2000

Effects of gonadotropin-releasing hormones, corticotropin-releasing hormone, and vasopressin on female sexual behavior.

The effects of intracerebroventricular (icv) infusion of four neuropeptides on female sexual behavior were examined in the female musk shrew (Suncus murinus). In the first experiment, (icv) infusion of 100 ng of the mammalian form of gonadotropin-releasing hormone (mGnRH) facilitated rapid display of receptivity. Gonadotropin-releasing hormone-infused females had shorter latencies to rump present and tail wag, compared with controls. In a second experiment, icv administration of the other form of GnRH present in musk shrew brain, the chicken GnRH-II form, produced no changes in female behavior relative to the control condition. In Experiment 3, icv delivery of corticotropin-releasing hormone (CRH) facilitated female sexual behavior, relative to vasopressin and controls. The females treated with CRH had shorter latencies to display rump present, tail wag, and for the receipt of the first missed intromission compared with females in the other treatment groups. Vasopressin increased female scent marking relative to that of CRH-treated females. These data indicate that neurohormones of the hypothalamic-pituitary-gonadal and the hypothalamic-pituitary-adrenal axes can facilitate reproductive behavior in S. murinus.

Animals↗
PubMed1986

Reproductive potential in the older woman.

There is a definite increase in the number of women bearing children in the 30- and 40-year-old age groups. The total number of women who are 35 to 40 years of age in the United States is projected to increase 42% and the percent births to this age group is projected to increase 37%. This is apparently because of a trend to postpone childbearing and first birth due to women's career priorities, advanced education, control over fertility, financial concerns, late and second marriages, and infertility. Associated with this is an increase in visits to the infertility specialist for older women who have an intrinsic decrease in fecundity with advancing age. Although, on the average, a woman will not experience menopause until about 50 years of age, her effective childbearing period may stop almost a decade earlier. A woman in her late 30s and, especially, early 40s is at some disadvantage in terms of conception delay, ability to carry a chromosomally normal fetus until term, and risk of trisomic conception. Certain endocrinologic parameters have been identified for the woman entering the transition to menopause. Biologic aging of the hypothalamic-pituitary-ovarian axis is intertwined with changes in the endocrine milieu of the perimenopause and preperimenopause. Despite a clear association of decreased fecundity in older women due to multiple biologic and social influences, so long as the individual has regular cycles and essentially normal endocrine parameters, she should be a candidate for an expedited infertility workup and ovulation induction, if not more aggressive treatment. Her obstetric profile is much improved, except for an increase in congenital anomalies and chromosomal defects. Chorionic villus biopsy study or amniocentesis is advised in all cases, regardless of therapy.

Abortion, Spontaneous↗
PubMed1994

Utilization of prenatal diagnosis for cystic fibrosis over the past seven years.

OBJECTIVE: First trimester prenatal diagnosis (PD) by DNA analysis for cystic fibrosis (CF) has been available for parents of affected children since May 1986. METHODS: In a prospective study 37 couples with a single child affected by CF were investigated. Fathers and mothers were interviewed simultaneously, and their attitudes towards further childbearing and potential utilization of PD ascertained. Parental answers were treated as one. A 7-year follow-up allowed comparison between intended and actual behavior. RESULTS: At the time of the interview, 16 parents (43%) were determined to have further children. Nineteen parents (51%) said they would certainly or probably utilize PD in case of pregnancy. Their predominant reason for favoring PD was the strong desire to have a healthy child (47%). Among the 18 rejectors (49%) the fear of an unsolvable conflict in case of an affected fetus prevailed (39%). Twenty-four pregnancies actually occurred in 18 families. Utilization of PD was arranged in five (21%) and finally performed in four (17%) cases. CONCLUSION: Availability of PD does not substantially change the reproductive behavior of parents of children with CF. Reasons for this were multifactorial, with anticipated difficulty in deciding to continue or terminate pregnancy being predominant.

Cystic Fibrosis↗
PubMed2001

Oxytocin: who needs it?

The neuropeptide oxytocin has been implicated in the initiation of maternal behavior, based on studies in rats and sheep. Females in both of these species naturally avoid infants until parturition when they begin to show an intense interest in maternal care. Oxytocin pathways in the brain appear to be important for this transition from avoidance to approach of the young. Recent studies in mice with a null mutation of the oxytocin gene suggest a different scenario. These mice, which completely lack oxytocin, exhibit full maternal and reproductive behavior, except for a deficit in milk ejection. Apparently, oxytocin is not essential for maternal behavior in this species. Consistent with the role of oxytocin for the transition from avoidance to approach in rats and sheep, nulliparous mice show full maternal behavior and therefore do not require the peptide for the initiation of maternal care. The species differences in the behavioral effects of oxytocin are associated with profound species differences in the location of oxytocin receptors in the brain. Recent transgenic studies suggest that these species differences in the neuroanatomical distribution of oxytocin receptors may be a function of inter-species variation in the flanking region of the oxytocin receptor gene. So, who needs oxytocin? For maternal care, not mice and (possibly) other species, like primates, with promiscuous parental care. Most important, in considering the behavioral or cognitive functions of oxytocin, one cannot accurately extrapolate across species unless one knows the species have the same neuroanatomical location of oxytocin receptors.

Animals↗
PubMed2001

Polychlorinated biphenyl contamination and minisatellite DNA mutation rates of tree swallows.

The evidence that exposure to polychlorinated biphenyls (PCBs) leads to mutations is equivocal and controversial. Using multilocus DNA fingerprinting, we compared the mutation rate of tree swallows (Tachycineta bicolor) nesting at sites with high and low levels of contamination with PCBs. The upper Hudson River, USA, is highly contaminated with PCBs as a result of releases from two capacitor manufacturing plants in Hudson Falls and Fort Edward, New York, USA. Tree swallows nesting nearby have some of the highest known concentrations of PCBs in their tissues of any contemporary bird population (up to 114,000 ng PCB/g tissue). We found no difference in mutation rates between sites in New York with high PCB contamination and reference sites in Wisconsin, USA, and Ontario and Alberta, Canada, with known or presumably low levels of contamination. Thus, the mechanism behind altered reproductive behavior of tree swallows along the upper Hudson River is most likely physiological impairment, such as endocrine disruption, rather than mutation.

Animals↗
PubMed1984

Nuclear estradiol and cytosol progestin receptor concentrations in the brain and the pituitary gland and sexual behavior in ovariectomized estradiol-treated middle-aged rats.

We wished to determine whether the altered nuclear estradiol (E2) receptor concentrations in middle-aged rats can explain the diminished responsiveness to E2 observed in aging rats. Therefore, we measured receptor concentrations in various brain areas and the pituitary gland of young and middle-aged ovariectomized rats 2 and 4 days after implantation of Silastic capsules containing E2. To determine whether any observable changes had physiological consequences, we correlated age-dependent changes in E2 nuclear receptor concentrations with two E2-dependent parameters: cytosol progestin receptor levels in equivalent brain areas and pituitary gland and progesterone-facilitated reproductive behaviors. Young (3-4 months old) and middle-aged (10-12 months old) Sprague-Dawley rats were ovariectomized and received Silastic capsules containing E2 dissolved in oil 1 week later (day 0). Groups of rats were killed at 1200 h on either day 2 or day 4. Nuclear E2 and cytosol progestin receptor concentrations were assessed in a nuclear and cytoplasmic extract from the medial basal hypothalamus, preoptic area, amygdala, and pituitary gland. To test steroid-induced mating behavior, ovariectomized young and middle-aged rats were treated with E2-containing capsules for 2 or 4 days. At 0900 h progesterone (0.2 mg/kg BW) was injected sc and receptive and proceptive behaviors were observed when experienced males were introduced 4-6 h later. Two days after implantation of E2 capsules, middle-aged rats exhibited lower nuclear E2 receptor concentrations in the medial basal hypothalamus and preoptic area than young rats. By day 4, there were no significant age-related differences in any brain area or in the pituitary gland. Parallel age-related differences were observed in cytosol progestin receptor concentrations on day 2 but they were not evident by day 4. Similarly, middle-aged rats exhibited deficits in proceptive behavior, lordosis quotient, and lordosis quality score on day 2, but there were no differences compared to young rats on day 4. These data demonstrate that E2-induced nuclear E2 receptor concentrations are lower in selected areas of the brain of middle-aged rats. Such changes appear to be physiologically important because they are correlated with changes in E2-induced cytosol progestin receptor concentrations and steroid-induced behaviors. Furthermore, they may partially account for age-related differences in E2-induced LH surges on day 2.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1999

Breast cancer risk in monozygotic and dizygotic female twins: a 20-year population-based cohort study in Finland from 1976 to 1995.

This population-based study investigated the occurrence of breast cancer over a 20-year period in a cohort of monozygotic (MZ) and dizygotic (DZ) twins in Finland. Altogether, 13,176 female twins of known zygosity who were living in Finland at the end of 1975 were identified from the Finnish Twin Cohort Study and followed-up for cancer through the Finnish Cancer Registry for the years 1976-1995. Standardized incidence ratios (SIRs) were calculated, based on national cancer incidence rates. The relative risk of breast cancer for MZ twins compared to DZ twins was decreased [SIR(MZ)/SIR(DZ) ratio = 0.78; 95% confidence interval (CI), 0.58-1.0]; the decreased risk for MZ twins (SIR = 0.76; 95% CI, 0.58-1.0) accounted for this result, whereas the risk for DZ twins did not differ from the general population risk (SIR = 0.98; 95% CI, 0.84-1.1). There was no risk decrease among MZ twins in other cancers related to reproductive behavior; i.e., number of children and age at first birth seem not to explain the decreased risk of breast cancer. Our results, which are in line with earlier studies on the same topic, suggest that prenatal influences or postnatal behavioral factors may protect MZ female twins from breast cancer.

Adolescent↗