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Hypothalamic sites of progestin action on aggression and sexual behavior in female Syrian hamsters.

The effects of intracranial implants of the synthetic progestin, promegestone (R5020), on aggression and sexual behavior were examined in female Syrian hamsters. Ovariectomized female hamsters showed high levels of aggression and no lordosis towards stimulus male and female hamsters, both prior to and after estradiol benzoate treatment. Forty-six hr after estradiol treatment (10 micrograms SC), 10% crystalline promegestone was applied bilaterally (27 ga cannulae) to the ventromedial hypothalamus. When tested 5-7 hr later, these animals had a significant reduction in the rate of attacks towards females, with no lordosis responding to a male. In contrast, promegestone in the caudal anterior hypothalamus activated low levels of lordosis, yet these females maintained high levels of aggression towards stimulus females. Females receiving promegestone in the rostral anterior hypothalamus, and control females receiving intracranial cholesterol, maintained high levels of aggression and no lordosis. Estradiol treatment alone enhanced pelvic movements in response to experimenter-applied perineal stimulation in a majority of females (18/22 compared with 4/22 prior to estradiol injection), with intracranial treatments having no further effect. These results indicate that progestins act on aggression and sexual behavior in female Syrian hamsters at different hypothalamic loci.

Aggression↗

Effects of estradiol on sexual receptivity, wheel-running behavior, and vaginal estrus in virgin prairie voles.

This study examined the effects of estradiol on sexual receptivity and vaginal estrus in experienced and virgin female prairie voles, and running wheel activity in virgin females. Because prairie voles undergo induced ovulation, we predicted that exogenous estradiol would not affect activity patterns nor stimulate lordosis in virgins. Females were SC injected with estradiol benzoate (ED) and placed with males, and sexual receptivity was monitored. In experienced females 0.5 micrograms of EB resulted in 100% of the females displaying lordosis after 48 h. In contrast, only 20% of the females receiving 0.05 micrograms displayed lordosis. Less than 20% of virgin females receiving EB displayed lordosis. Virgins displayed no change in wheel-running activity after EB treatments, indicating that behaviors that are influenced by estradiol and regulated by the brain may require previous exposure to males to develop. Although all females receiving the 0.5 micrograms of EB displayed vaginal estrus, virgin females achieved vaginal estrus later than experienced females, suggesting that exposure to males has a priming effect resulting in a reduced period to vaginal estrus.

Animals↗

Effects of the 5-HT1A agonist, 8-OH-DPAT, on sexual behaviors of the proestrous rat.

The effects of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), were examined in intact, proestrous rats. Although this compound has been reported to inhibit sexual receptivity of hormonally primed, ovariectomized rats, this is the first report of its effect in intact females. After intraperitoneal treatment with 8-OH-DPAT (0.01 to 0.25 mg/kg), there was a dose-dependent suppression of lordosis behavior. The inhibition occurred within 10-15 min after the higher doses and lasted at least an hour after treatment. When females were treated with 1 mg/kg trifluoromethylphenyl piperazine (TFMPP) 30 min prior to treatment with 0.1 mg/kg 8-OH-DPAT, females recovered more rapidly from the inhibitory effects of 8-OH-DPAT. After bilateral, intrahypothalamic infusion of 50 to 1000 ng 8-OH-DPAT, inhibition of sexual behavior resembled that seen following systemic treatment with 0.1 mg/kg 8-OH-DPAT, females recovered more rapidly from the inhibitory effects of 8-OH-DPAT. After bilateral, intrahypothalamic infusion of 50 to 1000 ng 8-OH-DPAT, inhibition of sexual behavior resembled that seen following systemic treatment. Cannula locations in the ventromedial hypothalamus, but not the posterior hypothalamus, produced rapid inhibition of lordosis behavior. Both the frequency and the quality of lordosis behavior were reduced within 5 to 10 min after bilateral infusion of 200 to 1000 ng (but not 50 ng) 8-OH-DPAT, and females often successfully avoided attempted mounts by the male. These results suggest that activation of ventromedial hypothalamic 5-HT1A receptors reduces lordosis behavior.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Oxytocin enhances, and oxytocin antagonism decreases, sexual receptivity in intact female rats.

In intact, non-ovariectomized female rats in spontaneous behavioral estrus, the i.c.v. injection of oxytocin significantly increased lordosis quotient and lordosis duration, starting from a dose of 1 ng/rat. On the other hand, the oxytocin antagonist, d(CH2)5Tyr(Me)-[Orn]8-vasotocin, injected at the same doses and by the same route, decreased lordosis quotient and lordosis duration, and prevented the effect of oxytocin. These data further support the notion that oxytocin plays a physiological role in female sexual receptivity.

Animals↗

Axon-sparing lesion of the preoptic area enhances receptivity and diminishes proceptivity among components of female rat sexual behavior.

Stereotaxic infusion of ibotenic acid deleted neurons in the medial preoptic area (POA) in the ovariectomized female rats. A well-circumscribed lesion was infiltrated by astrocytes; local axons of passage were spared. Following estrogen priming and progesterone supplement, the females with the lesion had higher lordosis quotients than the vehicle-infused controls, when males successfully mounted them. On the other hand, the treatment did not induce solicitation in females with the lesion nor reduced their rejection of male partners. Meanwhile, gradual and persistent suppression of the lordosis reflex followed electrical stimulation through electrodes placed in the POA lesion. Except that the females with the POA lesion needed less estrogen to obtain comparable prestimulation quotients with the controls, the lesioned and control animals responded similarly to the stimulation. Because an adjunct neural transection dorsal to the POA lesion abolished the stimulus-bound suppression of lordosis, the effect was due to the activation of axons of passage that presumably descend from the septum. It is concluded that the POA is the major target for estrogen in eliciting proceptive behavior; local POA neurons as well as septal efferents appear to inhibit the lordosis reflex, the principal receptive component in female rat sexual behavior.

Animals↗

Estrogen induction of sexual behavior in female rats and synthesis of polyadenylated messenger RNA in the ventromedial nucleus of the hypothalamus.

To test the hypothesis that estrogen stimulates sexual behavior by inducing transcription of polyadenylated messenger RNA, we studied the effects of cordycepin, an adenosine analog that disrupts polyadenylation, on the lordotic responses of ovariectomized female rats made sexually receptive with systemic injections of estradiol benzoate (EB) and progesterone (P). Cordycepin inhibited lordosis when infused into the ventromedial nucleus of the hypothalamus within an hour before the females received EB; its effectiveness varied linearly with dose. It did not significantly alter sexual behavior when infused into the medial preoptic area. A dose of cordycepin that decreased lordosis when infused 1 h before injection of 0.5 microgram EB did not affect the behavior when infused 1 h before injection of 500 micrograms P. Cordycepin does not suppress behavior by blocking estrogen uptake since it did not alter estrogen accumulation by hypothalamic cell nuclei. Cordycepin inhibits ribosomal RNA (rRNA) synthesis as well as polyadenylation. While this probably contributes to cordycepin's inhibitory effects on lordosis, it cannot fully account for them since a cytidine analog that inhibits rRNA synthesis without inhibiting polyadenylation did not mimic cordycepin's behavioral effects. Cordycepin may suppress synthesis of P receptors; however, this could not fully account for its behavioral effects since cordycepin also inhibited lordosis when the P receptor was bypassed by substituting methysergide for P. As assessed by protein synthesis autoradiography, cordycepin's effects are highly localized. The data support the notion that estrogen facilitates female sexual behavior by altering gene expression in the brain.

Animals↗

Sagittal knife cuts in the far-lateral hypothalamus reduce sexual receptivity in female hamsters.

We have previously shown that hypothalamic knife cuts confined to the sagittal plane lateral to the medial anterior hypothalamus-ventromedial nucleus can disrupt sexual receptivity in female golden hamsters. In the present study we have compared the effects of varying the lateral position of sagittal cuts located at this same rostral-caudal level. Near-lateral (NL) cuts were placed at or just lateral to the fornix, while far-lateral (FL) cuts were placed at the lateral edge of the medial forebrain bundle. Ovariectomized, estradiol benzoate plus progesterone-treated females were given weekly tests for lordosis before and after hypothalamic cuts. Changes in body weight and agonistic behavior were also recorded. Both NL and FL cuts reduced lordosis in response to both manual stimulation and a sexually active male. Postoperatively, it was more difficult to elicit lordosis from these females, and if elicited, the duration of the response was reduced. NL, but not FL, cuts also increased agonistic behavior, and produced obesity. Since both NL and FL cuts severed axons traveling in the region of the supraoptic commissures (SOC), these data support our hypothesis that these SOC connections are critical for sexual receptivity. The SOC carrys both efferents and afferents of the ventromedial hypothalamus. Sagittal-plane cuts which interrupt the SOC may disrupt lordosis by cutting either or both types of connection.

Agonistic Behavior↗

Acute estrogen potentiates excitatory responses of neurons in rat hypothalamic ventromedial nucleus.

In a previous behavioral study, brief application of a membrane-limited estrogen to neurons in rat hypothalamic ventromedial nucleus (VMN) facilitated lordosis behavior-inducing genomic actions of estrogen. Here, electrophysiological recordings from single neurons were employed to characterize these membrane-initiated actions. From rat hypothalamic slices, electrical activity was recorded from neurons in the ventrolateral VMN, the cell group crucial for estrogen induction of lordosis. In addition to the resting activity, neuronal responses to histamine (HA) and N-methyl-d-aspartate (NMDA) were also recorded before, during, and after a brief (10-15 min) application of estradiol (E, 10 nM). These two transmitters were chosen because their actions are mediated by different mechanisms: HA through G protein-coupled receptors and NMDA by ligand-activated ion channels. Vehicle applications did not affect either resting activity or neuronal responses. In contrast, acute E exposure modulated neuronal responses to transmitters, with no significant effect on the resting activity. It potentiated excitatory responses to HAs (20 out of 48 cells tested) and to NMDA (10 out of 19 cells), but attenuated inhibitory responses to HA (3 out of 6 units). Both of these hormonal actions would increase VMN neuronal excitation. In separate experiments, neuronal excitation was found to be suppressed by anesthetics, which would block E's induction of lordosis when administered at the time of estrogen application. These data are consistent with the notion that increasing electrical excitation of VMN neurons can be a mechanism by which acute E exposure facilitates the lordosis-inducing genomic actions of estrogens.

Animals↗

3alpha-hydroxy-5alpha-pregnan-20-one in the midbrain ventral tegmental area mediates social, sexual, and affective behaviors.

Progestins mediate the onset and duration of lordosis, the mating posture of female rodents, through actions in the hypothalamus and ventral tegmental area. In the hypothalamus, progesterone has traditional, "genomic" actions via intracellular progestin receptors. In the ventral tegmental area, 3alpha-hydroxy-5alpha-pregnan-20-one has "non-genomic" actions independent of progestin receptors to facilitate lordosis that involve GABA(A)/benzodiazepine receptors, NMDA type glutamate receptors, and/or dopamine receptors. 3alpha-Hydroxy-5alpha-pregnan-20-one levels also change with behavioral and/or environmental stimuli and may have a role in other reproductively-relevant behaviors, such as affiliation, exploration, and anxiety (socio-sexual behaviors). Data are reviewed that support the notion that: 1) effects of 3alpha-hydroxy-5alpha-pregnan-20-one in the midbrain ventral tegmental area facilitate lordosis and other reproductively-relevant behaviors. 2) 3alpha-Hydroxy-5alpha-pregnan-20-one, formed in the ventral tegmental area from metabolism of progestins, produced peripherally by endocrine glands, or centrally from biosynthesis in glial cells mediates socio-sexual behaviors. 3) 3alpha-Hydroxy-5alpha-pregnan-20-one's actions at GABA(A)/benzodiazepine receptors, NMDA type glutamate receptors, and dopamine receptors in the ventral tegmental area are important for lordosis; however, effects at these substrates on socio-sexual behaviors have not been elucidated. Given 3alpha-hydroxy-5alpha-pregnan-20-one's involvement in stress responses, its putative role as a homeostatic regulator and in the pathophysiology and treatment of neuropsychiatric disorders is discussed.

Affect↗

Effects of prenatal stress on sexual partner preference in mice.

Three-month old, male Swiss Webster mice were born to either control dams or dams who had been prenatally stressed with light, heat, noise and handling during the last week of gestation. As adults, male offspring were tested on sexual partner preference and sexual behavior (mounting, intromissions and lordosis) with a sexually experienced male stimulus animal and a stimulus estrous female. In comparison to males born to control dams, prenatally stressed males showed a sexual partner preference for the sexually active male as demonstrated by a negative partner preference score, more and longer visits to the male's compartment, fewer and shorter visits to the female's compartment and longer latencies to and lower frequencies of mounts and intromissions of females. In addition, stressed males showed a greater frequency of lordosis and a higher lordosis quotient than did control males. This study is the first to investigate the effects of prenatal stress alone, without hormonal manipulation, on sexual partner preference using both a partner preference paradigm and measures of sexual behavior such as mounting, intromissions and lordosis. These findings support the suggestion that prenatal stress alone is enough to significantly affect sexual partner preference in male mice.

Animals↗

The role of insulin-like growth factor-I and growth factor-associated signal transduction pathways in estradiol and progesterone facilitation of female reproductive behaviors.

We are examining the role of insulin-like growth factor-I (IGF-I) and downstream signal transduction pathways associated with growth factors (e.g., mitogen-activated protein kinase, MAPK) in estradiol and progesterone facilitation of female reproductive behavior in rats. Brain IGF-I receptor activity is required for the long-term, priming actions of estradiol on the female reproductive axis. Infusions of an IGF-I receptor antagonist during estradiol priming blocks induction of hypothalamic alpha(1B)-adrenergic receptors and luteinizing hormone surges, and attenuates lordosis behavior. Infusion of MAPK and phosphatidylinositol-3-kinase inhibitors inhibitors during estradiol priming completely blocks hormone-facilitated lordosis. Because progestin receptors (PRs) can be phosphorylated and activated by MAPKs, growth factor signaling pathways may also participate in progesterone facilitation of reproductive behaviors. Infusion of a MAPK inhibitor in estradiol-primed rats blocks progestin facilitation and sequential inhibition of lordosis and proceptive behaviors. Interference with MAPK signaling also inhibits behavioral responses to cGMP and a delta-opioid agonist, both of which can activate MAPK in some cells. Thus MAPK is involved in the facilitation of lordosis and proceptive behaviors, perhaps by phosphorylation of hypothalamic PRs.

Animals↗

Lumbosacral spine and pelvic inlet changes associated with pelvic organ prolapse.

OBJECTIVE: To determine the association between advanced pelvic organ prolapse and changes in lumbar lordosis and/or pelvic inlet orientation. METHODS: Lateral lumbosacral spine/pelvic x-rays were taken of women with grade 2 or greater uterovaginal prolapse and women with grade 1 or less prolapse standing in their usual upright posture. The angles of lumbar lordosis and the pelvic inlet were measured by a radiologist who was masked to the pelvic examination findings. RESULTS: Twenty women with prolapse were matched with 20 women without significant prolapse. There were no significant differences in the mean (+/- standard deviation [SDI) age (55.3 +/- 9.0 years compared with 53.4 +/- 9.5 years), body mass index (BMI) (28.9 +/- 5.6 compared with 28.4 +/- 5.2), gravidity (5.6 +/- 3.5 compared with 5.0 +/- 2.7), and vaginal parity (4.65 +/- 3.3 compared with 4.5 +/- 2.9) between the prolapse and nonprolapse groups, respectively. All participants were vaginally parous. The mean lumbar lordotic angle in women with pelvic organ prolapse (32.0 degrees +/- 9.8 degrees) was significantly lower than that of controls (42.4 degrees +/- 10.9 degrees) (P < .003). The mean angle of the pelvic inlet in women with pelvic organ prolapse (37.5 degrees +/- 7.0 degrees) was significantly larger than that of controls (29.5 degrees +/- 7.3 degrees) (P < .001). The differences in the mean angles of lumbar lordosis and the pelvic inlet, between the case and control groups, remained significant after multivariable logistic regression was performed. CONCLUSION: Women with advanced uterovaginal prolapse have less lumbar lordosis and a pelvic inlet that is oriented less vertically than women without prolapse.

Female↗

Anterior lumbar interbody fusion for the management of chronic lower back pain: current strategies and concepts.

In a retrospective analysis of two large multicenter clinical studies, 321 patients with degenerative lumbar disc disease were divided into two groups who underwent anterior lumbar interbody fusion using two threaded titanium fusion cages. To determine whether differences in surgical procedures and cage design affect anterior and posterior annular distraction and clinical outcomes, the authors evaluated the clinical and radiographic outcomes of patients treated with a stand-alone ALIF procedure. End-plate preservation techniques were associated with improved anterior and posterior disc space distraction compared with standard end-plate preparation techniques. Similarly, the use of the LT-CAGE device led to greater improvements in restoration of segmental lordosis than did the use of standard cylindric cages. Furthermore, these surgical benefits resulted in improved clinical outcomes as early as 3 months and were maintained over a 2-year follow-up period in patients with improved postoperative disc space distraction and lordosis. Placing cylindric cages in a lordotic or trapezoidal disc space can be accomplished only through asymmetric reaming of the vertebral end plates. In a lordotic disc space, the posterior portion of the disc must be reamed more than the anterior portion. This over-reaming inhibits distraction of the posterior disc space and limits restoration of neuroforaminal height. Reduced reaming and symmetric reaming of the vertebral end plates enable the surgeon to restore anatomic segmental lordosis across the disc space. The tapered cage configuration aids in maintaining segmental lordosis. Anatomic restoration of disc space contours has an impact on a patient's outcome after stand-alone anterior interbody fusion surgery.

Adult↗

[Unfavorable influence of the dynamic neutralization system on sagittal balance of the spine].

PURPOSE OF THE STUDY: The dynamic neutralization system (Dynesis) has been proposed for the treatment of symptomatic lumbar discopathy. This system preserves the mobility of the instrumented vertebral segment and restores discal height by posterior distraction on pedicular screws, stabilization being ensured by compression on a spacer. The potential kyphosing effect of this system and the impact on sagittal morphology of the spine were analyzed. MATERIAL AND METHODS: Twenty-six patients were studied. Lateral x-rays of the lumbar spine in the upright position were obtained before and after the surgical procedure and at mean 9.5 +/- 3.3 months follow-up. Comparisons were made between the pre- and postoperative presentation with measurement of the pelvic and spinal sagittal parameters described by Duval-Beaupère: inclination of the pelvic segment on the sacrum, lordosis, and disc wedge angles at each level (particularly the instrumented levels). Sagittal morphology was assessed pre- and postoperatively. RESULTS: Mean kyphosing effect was 6 +/- 1.4 degrees, induced by the posterior distraction system. This accentuated the initial lumbar hypolordosis related to the degenerative disease. Comparison of the pre- and postoperative films revealed four types of sagittal reaction of the lumbopelvic segment: no modification (type A), significant loss of lordosis without change at the pelvis level (type B) or with compensatory pelvic retroversion (type C), accentuation of the lordosis with pelvic anteversion (type D). CONCLUSION: The dynamic neutralization system (Dynesis) can stabilize degenerative discopathy and protect the adjacent levels. Posterior distraction perturbs the initial hypokyphosis and can lead to pelvic compensation to achieve better dynamic balance. This loss of lordosis is however a cause of excessive mechanical stress on the lumbar structures and can lead to long-term degradation. Future developments of this dynamic system should take into account the essential factor of sagittal balance.

Adult↗

Reproductive behavioral responsiveness to noradrenergic stimulation in developing guinea pigs.

The stimulatory effects of ovarian hormones on sexual receptivity in guinea pigs may be mediated by norepinephrine. Juvenile females rarely exhibit steroid-induced receptivity and also respond poorly to the lordosis-enhancing action of alpha-noradrenergic receptor stimulation. This experiment was designed to chart the development of behavioral responsiveness to the alpha-noradrenergic agonist, clonidine, and to test the hypothesis that higher doses of estradiol and/or clonidine are required to stimulate lordosis in juvenile compared to adult guinea pigs. Ovariectomized females received estradiol benzoate (10 microg or 50 microg SC) 40-48 h before administration of clonidine (1 mg/kg or 5 mg/ kg IP) or saline at 14-17-day intervals. Regardless of treatment, few animals (0-36%) displayed lordosis at 20, 34, or 48 days of age. At 65 days of age, in both estradiol dose groups significantly more clonidine- (1 mg/kg) than saline-injected animals displayed lordosis (80-91 vs. 0-33%, respectively). Clonidine (5 mg/kg) was ineffective at all ages. These data do not support the hypothesis that behavioral responsiveness to alpha-noradrenergic receptor stimulation in immature females can be elicited by increasing the doses of estradiol and/or clonidine. These results suggest the occurrence of a maturational change in the neural systems governing noradrenergic involvement in steroid-induced sexual behavior in guinea pigs.

Adrenergic alpha-Agonists↗

Female gonadal hormones, serotonin, and sexual receptivity.

The inhibitory and facilitatory effect of serotonergic (5-HT) receptor agonists and antagonists on the female rat lordosis reflex is reviewed. Emphasis is placed on the role of 5-HT(1A) and 5-HT(2) receptors. The effect of estrogen and progesterone on the lordosis response to 5-HT receptor-selective compounds is reviewed and potential mechanisms for hormonal modulation of the 5-HT system are suggested. Evidence that 5-HT modifies the female's position relative to a threshold for lordosis is presented. Finally, it is hypothesized that 5-HT's dual regulation of lordosis contributes to the female's ability to regulate mating behavior so that it occurs under physiological and environmental conditions that are conducive for individual, as well as species, survival.

Animals↗

Estrogen modulation of opioid and cholecystokinin systems in the limbic-hypothalamic circuit.

The display of lordosis behavior has been correlated with the estrogen-induced expression of cholecystokinin (CCK) and enkephalin within the limbic-hypothalamic circuit. These neuropeptides have opposing effects on lordosis; for example, in the medial preoptic nucleus, CCK facilitates and opiates inhibit lordosis. Antisense oligodeoxynucleotide blockade of receptor expression indicated that CCK modulates lordosis in the medial preoptic nucleus through the CCK(A)-receptor. Sequence-specific antibodies directed against delta- and mu-opiate receptor proteins labeled fibers in the medial preoptic nucleus. Estrogen treatment of ovariectomized rats or etorphine (a nonselective opiate agonist) treatment altered the appearance of the immunoreactivity from a diffuse pattern to one of distinctly stained mu-opiate receptor immunoreactive cells and varicose fibers in the medial preoptic nucleus. Such a pattern of staining reflects an internalization of mu-opiate receptors following agonist stimulation. This type of internalization has been used as an indication of synaptic activity. The distribution of receptor internalization surrounds the distribution of CCK cells in the medial preoptic nucleus, suggesting that endogenous opioid peptides may modulate estrogen-induced CCK mRNA expression. Interestingly, nonselective and delta-opiate receptor selective antagonists potentiated the estrogen-induced CCK mRNA expression in the medial preoptic nucleus. Together, these results suggest that endogenous opioid peptides may modulate the estrogenic upregulation of CCK mRNA expression and demonstrate an important level of regulation of gene expression in which synaptic activity modifies hormonal input.

Animals↗

Light-dark differences in behavioral sensitivity to oxytocin.

Ovariectomized female rats treated with estradiol benzoate (EB) and progesterone (P) were infused intracerebroventricularly with a low (200 ng) or high (1 microgram) dose of oxytocin (OT). The low dose of OT facilitated lordosis behavior only during the dark phase of the light-dark cycle in females that were pretreated with low doses of EB (2 micrograms) and P (250 micrograms). In contrast, the high dose of OT facilitated lordosis behavior during both the light and the dark phases but only in long-term ovariectomized females that were primed with large amounts of EB (2 x 10 micrograms) and P (500 micrograms). In females that were primed with lower amounts of ovarian steroids, the high dose of OT failed to increase levels of lordosis responding in either the dark or light phase. Thus, when female rats are treated with physiological amounts of ovarian hormones and OT, they are more sensitive to the facilitative effects of the OT on lordosis behavior during the dark phase.

Animals↗