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Striatal dopamine release stimulated by amphetamine or potassium: influence of ovarian hormones and the light-dark cycle.

The release of endogenous dopamine (DA) from rat striatal tissue was studied in an in vitro superfusion system following hormonal manipulations in vivo. Progesterone treatment in estrogen-primed ovariectomized female rats potentiated DA release stimulated either by amphetamine or potassium (K+). In addition, the amount of striatal DA released in response to K+-stimulation was influenced by the light-dark cycle. We conclude that striatal DA release is modulated by ovarian hormones, and suggest that ovarian hormone modulation of presynaptic striatal DA activity may contribute to well-known estrous cycle dependent variations in some non-reproductive behaviors.

Animals↗

Estradiol and progesterone influence L-5-hydroxytryptophan-induced myoclonus in male guinea pigs: sex differences in serotonin-steroid interactions.

The effects of castration in males and sex differences in the effects of estradiol and progesterone on L-5-hydroxytryptophan (L-5-HTP)-induced myoclonus in guinea pigs were examined. Castration had no effect on L-5-HTP-induced myoclonus in males. There were sex differences in sensitivity to L-5-HTP. In the absence of steroids, L-5-HTP-induced myoclonus was higher in gonadectomized males than females. A low dose of estradiol benzoate (EB; 3.5 micrograms) given 46 h before L-5-HTP (100 mg/kg) enhanced myoclonus in gonadectomized females but not males. However, at a higher dose of EB (10 micrograms) and a lower dose of L-5-HTP (80 mg/kg), myoclonic responding was enhanced in males. These findings indicate that estradiol has a similar effect on L-5-HTP-induced myoclonus in males and females, but do not rule out the possibility of sex differences in sensitivity to L-5-HTP when both sexes are given estradiol priming. When L-5-HTP was given 6 h after 0.5 mg progesterone in estradiol-primed males, myoclonus was enhanced. Progesterone treatment reverses the facilitative effect of EB on L-5-HTP-induced myoclonus in females. Therefore, progesterone has opposite effects on L-5-HTP-induced myoclonus in males and females. These findings were discussed with respect to the interaction of steroids and 5-HT transmission in the regulation of steroid-dependent reproductive behavior.

5-Hydroxytryptophan↗

Estrogen effects on neuronal responsiveness to electrical and neurotransmitter stimulation: an in vitro study on the ventromedial nucleus of the hypothalamus.

To investigate the effects of estrogen on the activity of the neurons in the hypothalamic ventromedial nucleus (VMN), the single-unit activity was recorded from in vitro brain tissue slices prepared from ovariectomized rats that were either treated or untreated with estrogen. In tissue slices continuously perifused with estrogen-free solution, half of the 348 VMN neurons studied were silent or nearly silent, and the rest fired spontaneously at low rates. Electrical stimulation of the periventricular region medial to the VMN evoked not only 3 types of orthodromic responses, but also antidromic responses from many VMN neurons, indicating that the VMN and the periventricular region are intimately and reciprocally connected. Neuronal responses to a battery of 6 neurotransmitters were studied by microinjecting 50 microliters of a transmitter solution directly into the chamber where the tissue slice was being continuously perifused. When effective, glutamate (Glut) was almost exclusively excitatory; acetylcholine (ACh) and norepinephrine (NE) could be excitatory and/or inhibitory; 5-hydroxytryptamine (5-HT) and dopamine (DA) were predominantly inhibitory; and gamma-amino-butyric acid (GABA) was exclusively inhibitory on neuronal activity. The overall resting neuronal activity and responses to the transmitter were very similar to those observed in in vivo studies, indicating that, for VMN at least, in vitro tissue slices can serve as a simplified model for studying neuronal activity and responses. Comparisons of results between estrogen-treated and untreated preparations showed that chronic, in vivo estrogen treatments, while having no effect on resting firing rate, selectively facilitated the responsiveness of silent (but not spontaneously active) neurons to excitatory orthodromic inputs, and the responsiveness to the excitatory action of ACh, the overall action of NE and the inhibitory action of 5-HT. These selective estrogen effects would no doubt alter the input-output relationships of VMN neurons evoked by the orthodromic inputs and ACh, NE and 5-HT. Since the VMN is crucial to many biological functions, and the cholinergic, adrenergic and serotonergic inputs to the ventromedial hypothalamus are involved in the estrogenic regulation of sexual behavior, reproductive neuroendocrine, and other biological functions, the alteration of the input-output relationships evoked by the orthodromic and transmitter inputs would affect the regulation of many functions.

Acetylcholine↗

Anatomical and electrophysiological evidence for a projection from the medial preoptic area to the 'mesencephalic and subthalamic locomotor regions' in the rat.

There is considerable physiological evidence indicating that the medial preoptic area plays an important role in neural circuits mediating ingestive, thermoregulatory, and reproductive behaviors, all of which involve foraging. The current series of anatomical and electrophysiological experiments was therefore designed to characterize a direct projection from the medial preoptic area to a region in the zona incerta just dorsal to the subthalamic nucleus, which appears to lie within the 'subthalamic locomotor region', and to the pedunculopontine nucleus, which lies within the 'mesencephalic locomotor region'. First, implants of the fluorescent tracer True blue were placed in the pedunculopontine nucleus, and retrogradely labeled neurons were consistently found in dorsal regions of the medial preoptic nucleus, anteroventral preoptic nucleus, rostral tip of the medial preoptic area, lateral parts of the medial preoptic area, and median preoptic nucleus. Second, combined retrograde-immunostaining experiments indicated that a small number of galanin-stained neurons in the rostral tip of the medial preoptic area project to the pedunculopontine nucleus, whereas in nearby regions some galanin- or neurotensin-stained neurons in the lateral preoptic area, and some neurotensin-stained neurons in the substriatal gray appear to project to the pedunculopontine nucleus, as do some neurotensin- or corticotropin releasing factor (CRF)-stained cells in the bed nucleus of the stria terminalis. Third, injections of the anterograde tracer Phaseolus vulgaris leukoagglutinin (PHA-L) into various parts of the medial preoptic area all labeled axons with terminal boutons in the caudal zona incerta and pedunculopontine nucleus. Fourth, single-pulse stimuli were delivered to the zona incerta and pedunculopontine nucleus and the location of antidromically activated neurons in the medial preoptic area was mapped using extracellular recordings. Somewhat less than one-third of the cells recorded from in the medial preoptic area were antidromically activated from either site and some 14% were influenced from both sites. The application of a reciprocal collision test to a small number of neurons suggested that at least some neurons in the medial preoptic area may send collaterals to both sites. And fifth, injections of procaine into the zona incerta were shown to block the antidromic activation of medial preoptic neurons by single-pulse stimulation of the pedunculopontine nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Changes in the activity of testosterone-metabolizing enzymes in the brain of male and female zebra finches during the post-hatching period.

The kinetic properties of the testosterone-metabolizing enzymes were studied in the hypothalamus of adult and young zebra finches of both sexes. Estradiol, 5 alpha-dihydrotestosterone, 5 beta-dihydrotestosterone and 5 beta-androstane-3 alpha,17 beta-diol were identified as metabolites of testosterone in males and females at different ages between 5 days post-hatch and adulthood. During maturation, the maximum velocity (Vmax) of the aromatase and 5 beta-reductase decreased in males and females while the affinity of these enzymes for the substrate increased (decrease in km). These changes were more pronounced for 5 beta-reductase than for aromatase. The affinity change of the 5 beta-reductase occurred progressively during the post-hatching development between 5 and 30 days and is thus probably a true developmental process. In the case of the aromatase, the change in affinity occurred much later (after 30-40 days) and is thus probably related to the sexual maturation. These kinetic changes during development are directly related to the roles played by testosterone and its metabolites, in particular estradiol, in the differentiation and activation of reproductive behavior in the zebra finch. In particular, the dramatic decrease in 5 beta-reductase activity during sexual maturation should correspond to a potentiation of testosterone action in the brain.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Prodynorphin- and substance P-containing neurons project to the medial preoptic area in the male Syrian hamster brain.

To determine if substance P- or prodynorphin-containing neurons of the medial nucleus of the amygdala and medial bed nucleus of the stria terminalis send projections to the medial preoptic area in the male Syrian hamster, we placed a fluorescent retrograde tract tracer (either Fluoro-gold, or rhodamine- or fluorescein-impregnated latex microspheres) into the medial preoptic area. Five to seven days later, the animals were treated with colchicine, allowed to survive for 48 h and the brains were processed for immunofluorescence histochemistry. Tissue sections were incubated in either rat anti-substance P or rabbit anti-C-peptide (the C-terminal sequence of dynorphin B) antiserum followed by incubation in either fluorescein- or rhodamine-conjugated anti-rabbit or anti-rat antiserum. When the injection site of retrograde tracer was centered within the caudal one-third of the medial preoptic area, labeled cell bodies were observed caudally in the medial part of the bed nucleus of the stria terminalis. Retrogradely labeled cell bodies were also observed in the posterodorsal subdivision of the medial nucleus of the amygdala. Both prodynorphin and substance P immunolabeling were observed in retrogradely labeled neurons in these two areas but fewer of these projection neurons were immunolabeled with substance P antiserum than with C-peptide antiserum. These projections may play a role in the peptidergic modulation of reproductive behavior in this species.

Amygdala↗

Sexually dimorphic concentrations of arginine vasotocin in sensory regions of the amphibian brain.

Arginine vasotocin (AVT) regulates reproductive behaviors in amphibians. We measured AVT in the brains of bullfrogs (Rana catesbeiana) and newts (Taricha granulosa) using radioimmunoassay. In bullfrogs, AVT concentrations were greater in males, compared to females, in the amygdala pars lateralis, optic tectum, and tegmentum. Concentrations in the dorsolateral nucleus were greater in females. In newts, AVT concentrations were also greater in the tectum and tegmentum of males. AVT may modulate dimorphic behaviors by acting at these sites.

Animals↗

Steroid priming promotes oxytocin-induced norepinephrine release in the ventromedial hypothalamus of female rats.

In vivo microdialysis was used to detect norepinephrine (NE) release in the ventromedial hypothalamus of estradiol (E2)- or E2 plus progesterone (P)-treated female rats injected with 1.0 IU of oxytocin (OXY). Dialysates were collected before and after OXY administration on 3 consecutive days and analyzed for NE content by high performance liquid chromatography with electrochemical detection. After the last sample was collected on day 1, animals were injected with 3 micrograms E2 benzoate or oil. On day 3, E2-primed animals received 200 micrograms of P and control females received oil prior to OXY administration. OXY administration did not induce NE release on day 1. When OXY was administered to animals that received E2 approximately 20 h earlier, increased release of NE was not consistently seen. In contrast, E2-primed animals that received P on day 3 displayed significant increases in the release of NE after OXY administration compared to their own basal levels and to NE levels in control animals. To distinguish whether E2 priming is sufficient to promote OXY-induced release of NE without the addition of P, NE content of VMH dialysates in a second group of animals was examined following exposure to vehicle or E2 alone. When OXY was administered 24 or 48 h after estrogen priming, only 1 of 4 E2-primed females had modestly elevated dialysate NE levels. To evaluate the interactions between OXY and NE in the regulation of reproductive behavior, lordosis responses were observed in hormone-primed female rats receiving systemic injections of OXY, the alpha 1-adrenoceptor antagonist prazosin, or both OXY and prazosin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Serotonergic lesions decrease mu- and delta-opiate receptor binding in discrete areas of the hypothalamus and in the midbrain central gray.

Serotonergic nerve terminals in the brain were lesioned by intraventricular infusion of the selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) and levels of mu- and delta-opiate binding were measured in brain areas implicated in reproductive behavior and gonadotropin secretion. The lesion decreased mu-receptor binding in the preoptic area (mPOA) and the midbrain central gray, while delta-receptor binding was decreased in the mPOA and the dorsomedial nucleus of the hypothalamus. Hypothalamic serotonergic lesions also attenuated morphine inhibition of female sexual behavior. These results indicate the existence of serotonergic-opiate interactions in select regions of the brain and suggest that these interactions may be important in the regulation of lordosis behavior.

Animals↗

Androgen concentration by a sexually dimorphic population of tachykinin-immunoreactive neurons in the rat ventral premammillary nucleus.

Strong connections with sexually dimorphic nuclei suggest that the ventral premammillary nucleus (PMv) may be involved in the mediation of reproductive behavior. Steroid autoradiography and immunohistochemistry were used to show that: (1) there is a sex difference in the numbers of PMv neurons that contain tachykinin peptides, (ii) dihydrotestosterone concentrating cells are densely distribution in the PMv and about a quarter of these also contain immunoreactive tachykinin and, (iii) size of the immunoreactive tachykinin population does not respond to alterations in levels of gonadal steroids in adulthood. Thus the PMv appears to make a contribution to the regulation of sexual behavior through androgen-concentrating, tachykinin-containing pathways that are anatomically distinct from estrogen receptive circuitry.

Androgens↗

Formation of connections between cultured identified neurones from the pleural ganglion of the pteropod mollusc Clione limacina.

A cluster of electrically interconnected neurosecretory cells (the 'white cells') involved in the control of reproductive behavior was identified in the right pleural ganglion of the marine mollusc, Clione limacina. Pleural ganglia also contain large neurons (PL1 and PL2) having no connections with each other and with the white cells. Most isolated white cells put into the simple unconditioned medium (50% L-15) adhered to the bottom of uncoated dishes and demonstrated neurite outgrowth for 7-10 days. If growing processes overlapped, the white cells formed electrical connections with each other, but they formed no connections with the PL1 and PL2 neurons. It is concluded that in the case which was under study cellular intrinsic properties were sufficient for the formation of 'correct' connections between neurones.

Animals↗

Role of oxytocin in the hypothalamic regulation of sexual receptivity in hamsters.

Oxytocin (OXT) has been implicated in the control of a variety of social and reproductive behaviors in several species. The purpose of the present study was to test the hypothesis that OXT activity within the medial preoptic-anterior hypothalamus (MPOA-AH) and the ventromedial hypothalamus (VMH) plays a critical role in the expression of sexual receptivity in Syrian hamsters. The first 2 experiments investigated whether OXT would stimulate sexual receptivity in female hamsters in a dose-dependent manner. A 3rd experiment investigated whether sexual receptivity would be inhibited when endogenous OXT activity was blocked. Microinjection of OXT into the MPOA-AH or the VMH induced sexual receptivity in a dose-dependent manner in ovariectomized (OVX) hamsters primed with estradiol. Microinjection of a selective OXT antagonist, d(CH2)5[Tyr(Me)2Thr4,Tyr-NH29] ornithine vasotocin into the MPOA-AH or the VMH significantly reduced the levels of sexual receptivity exhibited by OVX hamsters administered estradiol and progesterone. These findings support the hypothesis that OXT activity in the MPOA-AH and the VMH plays an important role in the regulation of sexual receptivity in hamsters.

Animals↗

The medullary reticular formation is a site of muscle relaxant action of diazepam on deep back and neck muscles in the female rat.

We tested the hypothesis that the effect of systemic injections of diazepam (DZ, 125 mg/kg) to reduce the quality of the reproductive behavior, lordosis, and to reduce the EMG of lumbar back muscles involved in lordosis (Schwartz-Giblin et al., 1984) is exerted through a reticulospinal pathway with cells of origin in the nucleus gigantocellularis that excites lumbar motoneurons indirectly (Robbins et al., 1990, Robbins et al., 1992). In contrast, DZ facilitates lordosis behavior when infused into the midbrain central gray (McCarthy et al., 1995). Direct deposits of crystalline mixtures of DZ (20-80 ng) in dextrose were delivered to the medullary reticular formation (MRF) by diffusion from a cannula inserted through a guide to which a bipolar stimulating electrode was attached. The multiunit EMG response evoked by 20 (300 ms long) stimulus trains was recorded in back and neck muscles, lateral longissimus and splenius before and 5, 15, 30 and 60 min after local DZ deposits. There was a significant reduction in EMG response over this time period when stimulus intensities were within the range of 1.2-1.5 times threshold (Friedman two-way non-parametric test, P < 0.002). Large amplitude motor units that provide large tensions were the most sensitive to DZ-induced inhibition. Control deposits of dextrose had no significant effect. Systemic injections of progesterone (1 mg, i.p.) 60 min after DZ deposits, but not after dextrose deposits, further reduced the MRF-evoked EMG responses over the course of 1 h. As predicted, DZ infusions into the midbrain central gray did not reduce the reticulospinal-evoked axial muscle response, consistent with the facilitatory effect of midbrain central gray infusions of DZ on the lordosis quotient. The results suggest that benzodiazepine agonists (if endogenous) acting at sites in the MRF would be effective muscle relaxants during pregnancy, prior to the fall in progesterone that precedes labor.

Animals↗

Morbidity risk among young adolescents undergoing elective abortion.

A cohort study comparing risks of morbidity at the time of elective abortion between 399 young adolescents aged 17 years or less matched to 399 women aged 20 to 29 years was completed. The study matched for duration of gestation, types of procedure, parity, race, month of procedure, and insurance status. Results indicated a relative risk of post-abortal endometritis for adolescents compared to older women of 2.5 (95% C.L. 1.48, 3.85). The reasons for this difference are unclear.

Abortion, Induced↗

Phase IV study of the injection Norigest in Pakistan.

A field study of the injectable contraceptive, norethisterone enanthate (NET-EN), was conducted in family planning clinics in Sind and Punjab provinces of Pakistan, to determine the acceptability and feasibility of providing NET-EN in government family planning clinics staffed by Family Welfare Visitors (FWVs). A total of 2147 women were recruited to the study, of whom approximately three-fourths had never previously used contraception. The overall discontinuation rate at one year was 78 per 100 women; the most common reason for discontinuation was bleeding disturbances, including amenorrhea, although returning to the clinic too late for an injection also accounted for a substantial proportion of the discontinuations. Given adequate training, FWVs were shown to be capable of providing NET-EN in family planning clinics, including managing the bleeding disturbances common with this method of contraception. No pregnancies were reported, demonstrating that the method is highly effective when used in a usual family planning clinic situation.

Adolescent↗

A comparative clinical trial of Norinyl 1/35 versus Brevicon in Rio Clara, Brazil.

A comparative clinical trial of two combined oral contraceptives (OCs) with equivalent estrogen content, but different amounts of progestogens, was conducted at the Centro Medico Especializado em Planejamento Familiar in Rio Clara, Brazil. The study was designed to determine the differences in discontinuation rates between Norinyl 1/35 (Syntex) and Brevicon (Syntex) as well as the frequency of selected side effects which might contribute to method discontinuation. Both OCs contain 0.035 mg of ethinyl estradiol; Brevicon contains 0.5 mg and Norinyl 1/35 contains 1 mg norethindrone. Three-hundred women enrolled in the study were randomly assigned to either the Norinyl 1/35 or Brevicon OCs and follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. Intermenstrual bleeding was reported by significantly more women in the Brevicon group than in the Norinyl group (p less than 0.05), and significantly more Brevicon users reported an increase in intermenstrual bleeding. At the end of the study period, no differences were found between the two OC groups in terms of discontinuation rates, but a large number of women in each group discontinued for menstrual problems. The total discontinuation rates at 11 months for both groups were extremely high: 68.2 for the Norinyl 1/35 group and 75.2 for the Brevicon users. The largest group of discontinuations were comprised of those discontinuing for menstrual problems, other personal reasons, planned pregnancy and side effects.

Adult↗

Effect of androgenic gland ablation on morphotypic differentiation and sexual characteristics of male freshwater prawns, Macrobrachium rosenbergii.

Mature males of the freshwater prawn, Macrobrachium rosenbergii (de Man), may change from one to another morphotype, according to a set sequence. Small males may develop into orange-claw males and orange-claw males into dominant blue-claw males. Each of the three morphotypes demonstrates distinctive reproductive behavior and secondary sexual characteristics. The role of the androgenic gland in this morphotypic transformation was examined experimentally by bilateral androgenic gland ablation (andrectomy) of small males and orange-claw males. For andrectomy initiated in the small male morphotype, transformation to the next morphotype was permitted (orange-claw), but subsequent transformation to the blue-claw morphotype was blocked. Andrectomy of orange-claw males did not prevent transformation into the blue-claw. Andrectomy on both small and orange-claw males caused disappearance of the genital papillae and atrophy of the sperm ducts and testes. The growth rates of the andrectomized small and orange-claw males were significantly lower than those of the unoperated and sham-operated controls. We conclude that androgenic gland factors control not only the differentiation of male secondary sexual characteristics but also morphotypic differentiation. Bioassays based on the results of this study will be instrumental in the characterization of such a factor(s).

Animals↗

Androgen and gonadotropin effects on male mate calls in South African clawed frogs, Xenopus laevis.

Mate calling is a prominent reproductive behavior of male South African clawed frogs. Calls consist of alternating slow- and fast-amplitude-modulated trills. Each trill is made up of a series of clicks. The effects of administration of exogenous gonadotropin and androgen on mate calling were studied in male Xenopus laevis. Males were paired with unreceptive female frogs to elicit maximal calling. The amount of time each animal spent calling during the testing period, the peak fundamental frequency of the calls, the rate of calling, and the interclick interval (ICI, a measure of the temporal patterning of the calls) were measured in intact, castrated, and hormone-replaced frogs. Injection of human chorionic gonadotropin (HCG) into intact frogs increased the amount of time spent calling and the ICI relative to measures taken after water injection. Castrated males did not call even when given HCG. Testosterone and dihydrotestosterone treatment reinstated calling in castrates and increased circulating levels of androgens. When androgen-replaced castrated males were injected with HCG, the amount of time spent calling increased and approached levels of intact, HCG-injected males. The above results suggest that androgens are necessary for the production of calls. Gonadotropins appear to play an important role in mate calling, a role at least partly independent of effects on testicular androgen synthesis.

Androgens↗