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PubMed1998

Reciprocal angulation of vertebral bodies in the sagittal plane in an asymptomatic Greek population.

STUDY DESIGN: A prospective study conducted on several roentgenographic parameters of the standing sagittal profile of the spine in an asymptomatic Greek population. OBJECTIVES: To perform segmental analysis of the sagittal plane alignment of the normal thoracic, lumbar, and lumbosacral spines and to compare the findings with those derived from similar populations. SUMMARY OF BACKGROUND DATA: Until recently, little attention has been paid to the sagittal segmental alignment of the spine, and there are only a few studies (in French and American populations) in which radiographic analysis of sagittal spinal alignment is investigated. METHODS: Ninety-nine consecutive asymptomatic Greek volunteers (38 men, 61 women), an average age of 52.7 +/- 15 years old (range, 20-79 years), were included in this prospective study, on the basis of several inclusion criteria. These volunteers were divided into six distinct age groups. The radiologic parameters, which were measured (by Cobb's method) on the lateral standing roentgenograms of the whole spine were: thoracic kyphosis (T4-T12), lumbar lordosis (L1-L5), total lumbar lordosis (T12-S1), distal lumbar lordosis (L4-S1), sacral inclination (measured from the line drawn parallel along the back of the proximal sacrum and the vertical line), pelvic tilting, vertebral body inclination, and relative segmental inclination between pairs of adjacent vertebrae. RESULTS: Thoracic kyphosis and lumbar lordosis (T12-S1, L1-L5) were not gender related. Thoracic kyphosis increased with age (P < 0.001), the lumbar spine (L1-L5) gradually became less lordotic as the thoracic kyphosis increased (P < 0.003), and total lumbar lordosis was not age related. Sacral inclination correlated strongly with both thoracic kyphosis (P < 0.002) and L1-L5 lordosis (P < 0.001). Pelvic tilting correlated strongly with L1-L5 lordosis (P < 0.0075), but did not correlate with thoracic kyphosis and age. Vertebral body inclination showed a narrow variability in T6-T12 and in L4 and a wide variability in T4, T5, L1-L3, and S1. Distal lumbar lordosis represents the 68.6% of the total lumbar lordosis. CONCLUSIONS: In the results of this study, a reliable table of reference for roentgenographic parameters in the sagittal plane of the spine was established in an asymptomatic Greek population. The parameters are similar to those used in previous studies. Thus, these data should be considered in preoperative planning and postoperative evaluation of achieved correction during restoration procedures of the spine in the sagittal plane.

Adult↗
PubMed2001

Lumbar sagittal alignment after fusion with a threaded interbody cage.

STUDY DESIGN: Records of 111 patients randomly selected from a population who received an interbody fusion cage during a clinical Investigation Device Exemption trial (BAK/L) yielded 126 operative levels and were retrospectively assessed. OBJECTIVES: This study examined lumbar spine sagittal alignment and clinical outcomes before and 2 years after fusion surgery. SUMMARY OF BACKGROUND DATA: Lumbar lordosis is important in spinal sagittal alignment and balance, especially the L4-S1 area. Perceived consensus is that anatomically correct lumbar lordosis is desired and that a loss of lumbar lordosis may lead to spine pathology. There is little information on lumbar lordosis after interbody fusion. METHODS: A random sample of 111 patients who received a cylindrical cage implant (total pool of 947 patients) yielded 126 operative lumbar segments. There were 52 posterior approaches and 59 anterior approaches, and all cages were placed in the L4-L5 or L5-S1 levels. Preoperative and 2-year follow-up lateral radiographs were measured for segmental lordosis. Cage position was measured relative to the posterior longitudinal ligament. Segmental lordotic change was correlated to clinical outcome at the 2-year follow-up. RESULTS: Preoperative lordosis was different as a function of surgical approach. There was a significant 2-year decrease in lordosis with the posterior approach group; however, all intervertebral angles were within typical ranges. Clinical outcomes were significantly improved 2 years postsurgery. There was no correlation between changes in lordosis and clinical outcomes. CONCLUSIONS: Interbody lumbar fusion with a threaded cylindrical cage does not appear to have any clinically relevant effects on segmental lordosis, which is maintained within anatomically normal levels. Clinical outcome measures show significant postsurgery improvement, and changes in lordotic angles are not predictive of clinical outcome.

Humans↗
PubMed2004

A longitudinal study of congruent sagittal spinal alignment in an adult cohort.

STUDY DESIGN: A 10+-year longitudinal study of 100 adult volunteers. OBJECTIVES: To identify congruent lumbar lordosis in association with other sagittal spinopelvic parameters. SUMMARY OF BACKGROUND DATA: The aging spine poses difficult problems in determining appropriate lumbar lordosis. The concept of congruent spinal alignment is preferred over that of normal spinal alignment, yet the definition of sagittal spinal congruity in elderly population has not been well documented. METHODS: A population-based recruitment of adult volunteers and follow-up of 10+ years was conducted. A total of 100 healthy volunteers with baseline age of 50+ years were subjected to standing entire spine radiographs. Radiologic parameters included lumbar lordosis, sacral inclination, sagittal spinal balance, and other sagittal alignments. RESULTS: Average age of the subjects was 62.0 years at baseline and 73.9 years at follow-up. Lumbar lordosis with <5 degrees change during observation was defined as stable lumbar lordosis (n = 34). Regression analyses of the baseline parameters revealed that sacral inclination was the sole predictor of stable lumbar lordosis (lumbar lordosis = 0.8 * sacral inclination, r = 0.94, P < 0.0001). Baseline lumbopelvic congruity, determined as 0.7 <or= lumbar lordosis/sacral inclination <or= 0.9, was associated with minimum alterations in sagittal spinal alignment, whereas subjects with incongruent lumbopelvic relationships were predisposed to developing kyphosis and spinal imbalance. CONCLUSIONS: Our study substantiates previous results showing that the strongest determinant of lumbar lordosis is sacral alignment. Appropriate lumbar lordosis was estimated to be 80% of sacral inclination using standing radiographs, and the proposed lumbopelvic congruity could measure stability in sagittal spinal alignment. This study provides practical data for the assessment of sagittal spinal alignment in the aging spine.

Adult↗
PubMed1993

Effects of clonidine and phentolamine infused into the medial preoptic area and medial basal hypothalamus of the guinea pig.

In ovariectomized (OVX) female guinea pigs sequential administration of estradiol and then progesterone (P) is usually necessary to induce the sexually receptive lordosis posture. Systemic administration of alpha-adrenergic agonists can induce lordosis in OVX guinea pigs primed with estradiol benzoate (EB) alone and facilitate lordosis in OVX females primed with EB and P. In this study, we examined the regional specificity of this regulation by infusing the alpha-adrenergic agonist clonidine (CLON) or the alpha-adrenergic antagonist phentolamine (PHEN) into discrete brain areas. CLON, infused in the medial basal hypothalamus (MBH) of EB-primed females, increased the percentage of females showing lordosis 15-45 min after infusion (p < 0.05) and also increased the number of seconds females held the lordosis posture 15 min to approximately 2.0 h after infusion (by as much as 65% at 15 min p < 0.001). CLON infused in the medial preoptic area (MPOA) of EB primed females had no effect on lordosis except at 4.0 h after infusion when it increased the number of seconds females held the lordosis posture (p < 0.05). In EB + P primed females, PHEN infused into the MBH transiently reduced the number of seconds EB + P primed females held lordosis from 30 min to approximately 2.0 h after infusion (by as much as 64% at 1.0 h; p < 0.01). Conversely, PHEN infused into the MPOA of EB + P primed females transiently increased the number of seconds females held lordosis from 15 min to 2.0 h after infusion (maximum difference 64%; p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1994

Nitric oxide mediates sexual behavior in female rats.

Nitric oxide (NO), an active free radical formed during the conversion of arginine to citrulline by the enzyme NO synthase (NOS), mediates vasorelaxation, cytotoxicity, and neurotransmission. Neurons containing NOS (NOergic) are located in the hypothalamus. These NOergic neurons control the release of several hypothalamic peptides. Release of NO from these NOergic neurons stimulates pulsatile release of luteinizing hormone-releasing hormone (LHRH) in vivo and LHRH release in vitro. LHRH not only induces LH release, which induces ovulation, but also facilitates female sexual behavior. Sexual behavior can be induced reliably in estrogen-primed ovariectomized female rats by progesterone (P). This behavior consists of proceptive behavior to attract the male and the assumption of a clear characteristic posture, lordosis, when mounted by the male. To ascertain the role of NO in the control of sexual behavior in female rats, an inhibitor of NOS, NG-monomethyl-L-arginine was microinjected into the third cerebral ventricle (3V) of conscious, ovariectomized, estrogen-primed rats with indwelling cannulae. NG-Monomethyl-L-arginine (10-1000 micrograms) prevented P-facilitated lordosis when administered intracerebroventricularly into the 3V, 20 min prior to the 3V injection of P. NG-Monomethyl-D-arginine, which does not inhibit NOS, did not inhibit lordosis under the same experimental conditions. Microinjection into the 3V of sodium nitroprusside (SNP), which spontaneously releases NO, facilitated lordosis in estrogen-primed rats in the absence of P. The facilitation of lordosis induced by either P or SNP was prevented by intracerebroventricular injection of hemoglobin, which binds NO. Lordosis facilitated by P or SNP was blocked by injection of LHRH antiserum into the 3V. The results are interpreted to mean that the P-facilitated lordosis response is mediated by LHRH release. Furthermore, since NO release from SNP also facilitates lordosis in the absence of P and this response could be blocked by LHRH antiserum, we conclude that P brings about the release of NO, which stimulates LHRH release that facilitates lordosis. Thus, the results indicate that NO induces LHRH release and that LHRH then plays a crucial role in mediation of sexual behavior in the female rats.

Amino Acid Oxidoreductases↗
PubMed2002

Changes in sagittal lumbar configuration with a new method of extension traction: nonrandomized clinical controlled trial.

OBJECTIVE: To determine if a new method of lumbar extension traction can increase lordosis in chronic low back pain (LBP) subjects with decreased lordosis. DESIGN: Nonrandomized controlled trial with follow-up at 3 months and 1(1/2) years. SETTING: Primary care spine clinic in Nevada. PATIENTS: Beginning in mid-1998, the first 48 consecutive patients, who met the inclusion criteria of chronic LBP with decreased lordosis and who completed the treatment program were matched for sex, age, height, weight, and pain scores to 30 control subjects with chronic LBP, who received no treatment. INTERVENTIONS: A new form of 3-point bending lumbar extension traction was provided in-office 3 to 4 times a week for 12+/-4 weeks. Per session, traction duration was started at 3 minutes and was increased to a maximum of 20 minutes. For short-term pain relief, torsion lumbar spinal manipulation was provided in the initial 3 weeks. MAIN OUTCOME MEASURES: Pain as measured on a visual analog scale (VAS) and standing lateral lumbar radiographic measurements. RESULTS: Pain scales and radiographic measurements did not change in the control subjects. In the traction group, VAS ratings decreased from mean +/- standard deviation of 4.4+/-1.9 pretreatment to 0.6+/-0.9 posttreatment (P<.001), and radiographic angles (except at T12-L1) showed statistically significant changes. Mean changes were 5.7 degrees at L4-5 (P<.001), 11.3 degrees between posterior tangents on L1 and L5 (P<.001), 9.1 degrees in Cobb angle at T12-S1 (P<.001), 4.6 degrees in pelvic tilt (P<.001), and 4.7 degrees in Ferguson's sacral base angle (P<.001). At long-term follow-up (17(1/2)mo), 34 of the 48 (71%) subjects returned. Improvements in lordosis were maintained in all 34. CONCLUSIONS: This new method of lumbar extension traction is the first nonsurgical rehabilitative procedure to show increases in lumbar lordosis in chronic LBP subjects with hypolordosis. The fact that there was no change in control subjects' lumbar lordosis indicates the stability of the lumbar lordosis and the repeatability of x-ray procedures. Because, on average, chronic LBP patients have hypolordosis, additional randomized trials should be performed to evaluate the clinical significance of restoration of the lumbar lordosis in chronic LBP subjects.

Adult↗
PubMed1999

The effect of operative position and short-segment fusion on maintenance of sagittal alignment of the lumbar spine.

STUDY DESIGN: A retrospective radiographic assessment of the maintenance of sagittal alignment in patients undergoing short-segment instrumented fusions in a knee-chest position. OBJECTIVE: To determine whether the use of the knee-chest position adversely effects the maintenance of lumbar sagittal alignment in patients undergoing short-segment instrumented fusions of the lumbar spine. SUMMARY OF BACKGROUND DATA: Previous authors have demonstrated that lumbar lordosis is reduced in the knee-chest position, but it is unknown whether the kneeling position adversely affects the maintenance of lumbar lordosis in short-segment instrumented fusions during the follow-up period. METHODS: Twenty-eight patients (17 men and 11 women, 20-72 years of age) were reviewed retrospectively, having undergone short-segment fusions in the kneeling position. Seven patients underwent posterior spinal fusion from L4 to L5, 13 patients from L5 to S1, and 8 patients from L4 to S1. Transpedicular instrumentation and autogenous iliac crest bone grafting was used in all cases. Radiographs were assessed for sacral tilt, lumbar lordosis, and intervertebral angulation. Data were analyzed with repeated measures analysis of variance. RESULTS: The minimum follow-up period was 33 months. For all 28 patients, lumbar lordosis measured 51 degrees before surgery, 37 degrees during surgery (P = 0.0001), and 50 degrees after surgery (P = 0.6135). In patients undergoing L4-S1 posterior spinal fusion, sacral tilt measured 49 degrees before surgery and 45 degrees after surgery (P = 0.039). Although overall lumbar lordosis was maintained, lordosis was shifted proximally in the lumbar spine, increasing at L1-L4 from 19 degrees before surgery to 24 degrees after surgery, while decreasing at L4-S1 from 32 degrees before surgery to 26 degrees after surgery. CONCLUSION: Overall lumbar lordosis is well maintained in patients undergoing short-segment instrumented fusion in the kneeling position. With compensatory lordosis being shifted proximally and sacral tilt not returning to the preoperative status in L4 to S1 fusions, caution should be exercised in using the kneeling position for longer instrumented lumbar fusions.

Adult↗
PubMed1999

Segmental roentgenographic analysis of vertebral inclination on sagittal plane in asymptomatic versus chronic low back pain patients.

Two homogenous groups of 120 volunteers and 120 low back pain (LBP) patients, age range 20-79 years, underwent a prospective roentgenographic segmental vertebral analysis of the thoracic and lumbar spine to compare several roentgenographic parameters useful for planning spine surgery. The following roentgenographic parameters were measured: thoracic kyphosis, lumbar lordosis, sacral inclination, distal lordosis (L4-S1), inclination of each vertebra from T4-S1, and relative vertebral inclination between adjacent vertebrae. Thoracic kyphosis increased (p < 0.0001) and sacral inclination decreased (p < 0.05) with age in the control group. Increased thoracic kyphosis correlated with decreased lumbar lordosis after the sixth decade in the control group (p < 0.01), less so in the LBP group (p < 0.05). Increased thoracic kyphosis was seen more in the LBP group than in the controls, but significantly solely in the sixth decade (p < 0.01). Lumbar lordosis was more increased in the controls than in the LBP group but significantly solely in the sixth decade (p < 0.001). The L5-S1 segmental lordosis was much more in the LBP patients than in the controls (p < 0.001). Lumbar lordosis was strongly correlated with sacral inclination in both groups (p < 0.0001) and it was significantly greater in the controls, particularly in the sixth decade (p < 0.001). Sacral inclination was significantly more in the female than in male volunteers (p < 0.05). Distal lordosis (L4-S1) represents 55% and 49% of total lumbar lordosis in controls and low back patients, respectively. Spine surgeons frequently deal with sagittal spinal deformities and the deviations of sagittal spinal curvatures and vertebral inclination in the sagittal plane, both in normal subjects and LBP patients should be clinically helpful.

Adult↗
PubMed2002

The effects of serotonin agonists on the hypothalamic regulation of sexual receptivity in Syrian hamsters.

One brain region that has been implicated in the regulation of lordosis is the medial preoptic-anterior hypothalamic continuum (MPOA-AH). Previous studies have suggested that this zone may be part of the circuit mediating the effects of serotonin (5-HT) on sexual receptivity. In the present experiments, we investigated the role of 5-HT(1a/7) and 5-HT(2) receptor subtypes in the MPOA-AH in the control of lordosis. In two experiments, either 5-HT(1a/7) or 5-HT(2) agonists were injected unilaterally into the MPOA-AH of ovariectomized, hormonally primed female hamsters. In the first experiment, microinjections of the 5-HT(1a/7) agonist 8-hydroxy-2,9-(di-n-propylamino)tetralin resulted in an attenuation of the lordosis posture by causing a decrease in the mean lordosis duration and an increase in the number of lordosis episodes over the entire testing period. In the second experiment, microinjections of the 5-HT(2b/2c) agonist m-chlorophenylpiperazine did not result in any changes in sexual receptivity. However, microinjections of the 5-HT(2) agonist (2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl facilitated lordosis by increasing the mean lordosis duration and decreasing the number of lordosis episodes in the first 5 min of the testing period. These data indicate that serotonin may act in the MPOA-AH via 5-HT(1a/7) receptors to attenuate and 5-HT(2) receptors to facilitate sexual receptivity.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1979

Noradrenergic transmission and female sexual behavior of guinea pigs.

Treatment with the dopamine beta-hydroxylase (DBH) inhibitor U-14,624 (50, 100, or 150 mg/kg) blocked the induction of lordosis behavior be estradiol benzoate (EB) and progesterone (P) in ovariectomized guinea pigs. After treatment with U-14,624 (100 mg/kg), norepinephrine (NE) content of medial basal hypothalamus, preoptic area and cortex was reduced (by 55%) and dopamine (DA) content of medial basal hypothalamus was increased (by 155%) during the period when females treated with EB and P normally display lordosis. Treatment with the NE receptor stimulator clonidine (1.0 mg/kg) restored lordosis behavior in females treated with EB, P, and U-14,624 (100 mg/kg), but the putative DA and serotonin (5-HT) receptor blockers pimozide (1.0 mg/kg) and methysergide (20.0 mg/kg) were ineffective in this respect. Thus, inhibition of lordosis after treatment with U-14,624 appeared to be attributable primarily to a reduction in NE neurotransmission, rather than to increase in DA or 5-HT activity. Because clonidine induced lordosis in females treated with EB, P, and U-14,624, it seemed unlikely that the facilitatory effects of clonidine on lordosis were mediated by activation of presynaptic alpha-adrenergic receptors (i.e. inhibitory NE autoreceptors) rather than by postsynaptic alpha-receptors. In addition, pretreatment with the postsynaptic alpha-adrenergic antagonist phenoxybenzamine (20.0 mg/kg) blocked the facilitation of lordosis by clonidine (1.0 mg/kg) in females primed with EB alone and with EB plus P. Thus, the facilitatory effects of clonidine on lordosis appear to be mediated by activation of postsynaptic alpha-adrenergic (i.e. NE) receptors. The results of this study provide further evidence that NE neurotransmission facilitates the expression of female sexual behavior in guinea pigs.

Animals↗
PubMed1990

Roles of the pontine dorsomedial tegmentum and midbrain central gray in regulating female rat sexual behaviors: effects of p-chlorophenylalanine.

Lesions in the midbrain dorsal central gray (MCGL) markedly suppressed both lordosis and soliciting behavior in estradiol benzoate-progesterone (EB-P)-primed castrated female rats. Similarly, the pontine dorsomedial tegmental lesions (PDMTL) caused a severe loss of lordosis behavior. However, the PDMTL females while demonstrating no lordotic response displayed ear-wiggling. These results suggest that the midbrain dorsal central gray plays an important role in regulation of both lordosis and soliciting behaviors. In contrast, the pontine dorsomedial tegmentum appears to participate in regulating the neural mechanism for lordosis only and not for soliciting behavior. Two weeks later prior to a second test, approximately half of the MCGL and PDMTL females that had shown no lordosis in the first test, were injected with p-chlorophenylalanine (PCPA) and primed with EB-P. PCPA significantly increased the lordotic activity of EB-P-primed MCGL females, whereas it failed to potentiate a lordotic response in the PDMTL females. Since PCPA effectively facilitated the display of lordosis in the absence of the neural substrate of the midbrain central gray, this neural structure may not be the minimally necessary component of the neural circuitry regulating the display of lordosis behavior. On the other hand, the pontine dorsomedial tegmentum may be a neural substrate more closely related with the descending pathway controlling the expression of lordosis.

Animals↗
PubMed2006

Progestins' effects on sexual behaviour of female rats and hamsters involving D1 and GABA(A) receptors in the ventral tegmental area may be G-protein-dependent.

In the ventral tegmental area (VTA), progestins have actions involving dopamine type 1-like receptors (D(1)) and gamma-aminobutyric acid (GABA)(A)/benzodiazepine receptor complexes (GBRs) for lordosis. Evidence suggests that D(1) and GBRs can have G-protein-mediated effects. We investigated if, in the VTA, inhibiting G-proteins prevents D(1)- and/or GBR-mediated increases in progestin-facilitated lordosis. Hamsters, with bilateral guide cannulae to the VTA, received systemic E(2) (10 microg) at hour 0 and progesterone (P, 250 microg) at hour 45. At hour 48, hamsters were pre-tested for lordosis and infused with the G-protein inhibitor, guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S, 50 microM/side), or 10% DMSO saline vehicle. Thirty minutes after initial infusions, hamsters were re-tested and then immediately infused with the D(1) agonist, SKF38393 (100 ng/side), the GBR agonist, muscimol (100 ng/side), or saline vehicle. Hamsters were post-tested for lordosis 30 min later. For rats, E(2) (10 microg) priming at hour 0 was followed by lordosis pre-testing at hour 44. After pre-testing, rats received infusions of GDP-beta-S or vehicle, followed by infusions of SKF38393, muscimol, or vehicle and then infusions of the neurosteroid, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP, 100 or 200 ng/side), or beta-cyclodextrin vehicle. Rats were tested immediately after each infusion of SKF38393, muscimol or vehicle, as well as 10 and 60 min after 3alpha,5alpha-THP or vehicle infusions. Inhibiting G-proteins, in the VTA, reduced the ability of systemic P or intra-VTA SKF38393 or muscimol to facilitate lordosis of E(2)-primed hamsters. Blocking G-proteins, in the VTA, prevented SKF38393-, muscimol- and/or 3alpha,5alpha-THP-mediated increases in lordosis of E(2)-primed rats. Thus, progestins' actions in the VTA for lordosis that involve D(1) and/or GBRs may also include recruitment of G-proteins.

Analysis of Variance↗
PubMed1997

5-HT3 receptors in the ventromedial nucleus of the hypothalamus and female sexual behavior.

Within the ventromedial nucleus of the hypothalamus (VMN), serotonin exerts a dual role in the control of female rat lordosis behavior. Most emphasis has been placed on 5-HT1A and 5-HT2 receptors, which inhibit and facilitate the behavior, respectively. In the current experiment, a potential role for VMN 5-HT3 receptors in the control of lordosis behavior was examined. Ovariectomized rats, hormonally primed with 25 microg estradiol benzoate and 500 microg progesterone, received bilateral VMN infusions with 100 ng, 250 ng or 500 ng of the 5-HT3 receptor antagonist, tropisetron. In these rats, there was a dose-dependent decline in both the lordosis to mount (L/M) ratio and in the quality of the lordosis reflex with 500 ng tropisetron producing the most consistent change in lordosis behavior. Relative to hormone-primed, ovariectomized rats, lordosis behavior of proestrous females was less affected by VMN infusions with the 5-HT3 receptor antagonist. The 5-HT3 receptor agonist, m-chlorophenylbiguanide (mCPBG), attenuated the effect of tropisetron; of the three mCPBG doses (500 ng, 1000 ng, 1500 ng) examined, 1000 ng was the most effective, perhaps because, alone, 1500 ng mCPBG slightly reduced lordosis behavior. These observations emphasize the potential role for VMN 5-HT3 receptors in the control of lordosis behavior.

Animals↗
PubMed1999

Progesterone has rapid and membrane effects in the facilitation of female mouse sexual behavior.

Ovariectomized (ovx) mice require both estradiol (E2) and progesterone (P) administration to reinstate feminine sexual behavior (lordosis). The importance of P's actions at E2-induced intracellular progestin receptors (PRs) to facilitate lordosis was investigated in PR knockout (PRKO) mice, PRKO's wild type littermates (C57X129), and wild type C57BL/6J (C57) mice. Subjects were ovx, E2-primed (0.5 microg) and tested following intravenous (i. v.) and intercereberal P. Intravenous P (200 microg) significantly increased lordosis of all mice within 10 min of P, but vehicle infusion did not (Experiment 1). Intravenous P significantly increased the amount and duration and reduced the latency of lordosis, over that seen with vehicle infusion, in PRKO and wild type mice. Whole brain concentrations of P and its 5alpha-reduced metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), which has low affinity for intracellular PRs, were also increased following P compared to vehicle infusion. Progesterone, but not vehicle infusions, significantly increased the number of PR-immunoreactive (PR-IR) cells in the ventromedial hypothalamus (VMH) of C57 and C57X129 mice and increased number of 3alpha, 5alpha-THP-immunoreactive (3alpha,5alpha-THP-IR) cells in the ventral tegmental area (VTA) of all mice. In Experiment 2, P conjugated to bovine serum albumin (P:BSA) increased lordosis when applied bilaterally to both the VMH and VTA of E2-primed mice more than BSA implants. Progesterone implants increased the number of PR-IR cells in the VMH of C57 and C57X129 mice and the number of 3alpha,5alpha-THP-IR cells in the VTA of all mice. The rapid facilitation of lordosis with i.v. P infusion and increases in lordosis when P's effects are relegated to the membrane in the VMH and VTA of PRKO and wild type mice suggest that P may facilitate lordosis through actions at substrates other than intracellular PRs. The present findings suggest a role of 3alpha,5alpha-THP.

Animals↗
PubMed2001

The role of neurosteroids and non-genomic effects of progestins and androgens in mediating sexual receptivity of rodents.

Progestins and androgens modulate sexual receptivity in rodents, in part through mechanisms independent of traditional intracellular steroid receptors. Progesterone (PROG) in the ventromedial hypothalamus (VMH) and ventral tegmental (VTA) facilitates lordosis but has different actions in these brain areas. Primarily using lordosis in rodents as an in vivo experimental model, we have examined the effects that progestins exert in the midbrain and hypothalamus. Localization and blocker studies indicate that PROG's actions in the VMH require intracellular progestin receptors (PRs) but in the VTA they do not. Progestins that have rapid, membrane effects, and/or are devoid of affinity for PRs, facilitate lordosis when applied to the VTA. Manipulation of GABA and/or GABA(A)/benzodiazepine receptor complexes (GBRs) in the VTA alters lordosis, which suggests that progestins may interact with GBRs to facilitate receptivity by enhancing the function of GABAergic neurons. Interfering with PROG's metabolism to, or the biosynthesis of, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-TH PROG or allopregnanolone), the most effective endogenous GBR agonist, in the VTA attenuates female sexual behavior in rodents. Stimulation of mitochondrial benzodiazepine receptors (MBRs), which enhances neurosteroid production, by infusions of an MBR agonist to the VTA enhances lordosis. 3alpha,5alpha-TH PROG is increased in the midbrain of mated>proestrous>diestrous rodents. These data suggest that in the VTA, PROG may facilitate lordosis following metabolism to and/or biosynthesis of 3alpha,5alpha-TH PROG, which may have subsequent actions at GBRs and/or MBRs to acutely modulate female sexual behavior in rodents. The 3alpha-hydroxysteroid oxidoreduced metabolite of dihydrotestosterone (DHT), 5alpha-androstane-3alpha,17beta-diol (3alpha-androstanediol), is important for termination of sexual receptivity in rodents and has these effects in the absence of functional intracellular androgens receptors. As well, altering GBR function in the hypothalamus can influence 3alpha-androstanediol's inhibition of sexual receptivity. Through actions in the hypothalamus that are independent of intracellular androgen receptors but involving GBRs, 3alpha-androstanediol inhibits lordosis. These findings suggest that the PROG metabolite and pregnane neurosteroid, 3alpha,5alpha-TH PROG, and the testosterone metabolite and androstane neurosteroid, 3alpha-androstanediol, can have proximate influences on lordosis that is via nonclassical actions at intracellular steroid receptors.

Androgens↗
PubMed1987

Antagonism of sexual behavior in female rats by ventromedial hypothalamic implants of antiestrogen.

The present experiments sought to identify brain regions in which implants of an antiestrogen would antagonize the ability of a systemic estradiol treatment to activate sexual behavior in female rats. In experiment 1, ovariectomized female rats were implanted subcutaneously with 5-mm Silastic capsules containing a 5% concentration of estradiol and injected with 500 micrograms progesterone 2 days later, 4-5 h before testing for sexual behavior. Bilateral intracranial implants of 1% crystalline concentrations of the high-affinity antiestrogens monohydroxytamoxifen (TAM) or keoxifene placed into the ventromedial nucleus of the hypothalamus (VM) 24 h prior to estradiol treatment significantly reduced lordosis responsivity compared with control females receiving empty cannulae. Implants of 1% TAM into the medial preoptic area or medial amygdala 24 h prior to estradiol that no significant effect on lordosis. Similarly, implants of 1% TAM into the VM 12 h after estradiol had no effect on lordosis. In experiment 2, lordosis was activated by subcutaneous implants of Silastic capsules containing 1% estradiol plus 500 micrograms progesterone. In this experiment, implants of 1% TAM into the VM 24 h prior to estradiol significantly reduced lordosis only if both cannulae tips were in, or adjacent to, the VM. Females receiving intracranial 1% TAM, but whose cannulae (even unilaterally) were outside the VM, had levels of lordosis equivalent to those of control females. Increasing the concentration of intracranial TAM to 10% virtually eliminated lordosis in females with bilateral implants in the VM, whereas females receiving intracranial 10% TAM in the region of, but outside, the VM showed no evidence of a lordosis deficit.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Participation of growth factor signal transduction pathways in estradiol facilitation of female reproductive behavior.

Estradiol (E(2)) regulates female reproductive behavior (lordosis) by acting on estrogen-sensitive neurons. We recently showed that E(2) facilitation of lordosis behavior requires concurrent activation of brain IGF-I receptors. The present study confirmed this finding and sought to identify the downstream signaling pathways involved in estrogen/IGF-I priming of lordosis. Intracerebroventricular infusions of a selective IGF-I receptor antagonist were administered to ovariectomized rats every 12 h beginning 1 h before the first of two daily E(2) injections. IGF-I receptor blockade partially inhibits lordosis if the antagonist is infused throughout the 2-d estrogen treatment period but not if it is administered only during the first or last 12 h of estrogen treatment. Because E(2) and IGF-I can activate phosphatidylinositol-3-kinase (PI3K) and MAPK, we infused agents that block PI3K and/or MAPK activity as described above. Both PI3K inhibitors (wortmannin and LY294002) and MAPK inhibitors (PD98059 and U0126) partially attenuate lordosis when administered during estrogen priming. None of these drugs modifies lordosis if they are infused only once, during the last 12 h of estrogen treatment. When both wortmannin and PD98059 are infused during E(2) priming, lordosis behavior is completely abolished. These data suggest that activation of both PI3K and MAPK by E(2) and IGF-I mediates hormonal facilitation of lordosis behavior.

Animals↗
PubMed2002

The role of rigid vs. dynamic instrumentation for stabilization of the degenerative lumbosacral spine.

PURPOSE OF THE STUDY: This is a prospective comparative randomised study to compare the immediately postoperative effects of a rigid versus dynamic instrumentation for degenerative spine disease and stenosis on the standing sagittal lumbar spine alignment and to investigate if a dynamic spine system can replace the commonly used rigid systems in order to avoid the above mentioned disadvantages of rigid fixation. MATERIAL & METHODS: 15 randomly selected patients received the rigid instrumentation SCS and an equal number of randomly selected patients the dynamic TWINFLEX device for spinal stenosis associated degenerative lumbar disease. The age of the patients, who received rigid and dynamic instrumentation was 65 +/- 9 years and 62 +/- 10 years respectively. All patients had standing spine radiographs preoperatively and three months postoperatively. The parameters that were measured and compared pre- to postoperatively were: lumbar lordosis (L1-S1), total lumbar lordosis (T12-S1), sacral tilt, distal lordosis (L4-S1), intervertebral angulation, vertebral inclination and disc index. RESULTS: The instrumented levels in the spines that received rigid and dynamic instrumentation were 3.5 +/- 0.53 and 3 +/- 0.7 respectively. The instrumented levels from L3 to L5 were 23, the lumbosacral junction was instrumented in 3 patients of group A and in 4 patients of group B. Lumbar lordosis did not significantly change postoperatively, while total lordosis was significantly (P=0.04) increased in the patients who received the rigid instrumentation, while it was significantly (P=0.012) decreased in the group B. Intervertebral angulation of the non-instrumented level L1-L2 was increased in the group A (P=0.01), while the dynamic instrumentation increased (P=0.02) the intervertebral inclination of the adjacent level L2-L3, immediately above the uppermost instrumented level. Distal lordosis and sacral tilt did not change in any patient in both groups. Both instrumentations did not change the lateral vertebral inclination of L1 to L5 vertebrae. Rigid instrumentation increased the lordotic inclination of L5 (P=0.03) and of S1 (P=0.03). Rigid instrumentation increased (P=0.04) the intervertebral angulation at the uppermost instrumented level L3-L4 The most significant change in vertebral angulation was achieved at the instrumented level L4-L5 by the dynamic (P=0.007) and rigid (0.05). The disc index at the level L2-L3 was increased by both instrumentation [dynamic P=0.007 and rigid (P=0.02)]. The index L3-L4 was increased following dynamic fixation (P=0.0007). The disc index L4-L5 was postoperatively increased by both types of instrumentation (rigid P=0.006, dynamic P=0.02). The disc index L5-S1 did not significantly change postoperatively by either system. CONCLUSION: Both rigid and dynamic instrumentations restored lumbar lordosis, sacral tilt, distal lordosis and increased the foraminal diameter at the level L4-L5 resulting in an indirect decompression of the nerve roots at this level . Both rigid and dynamic instrumentations applied in the lumbosacral spine to treat degenerative disease secured L3 to S1 sagittal spine profile close to preoperative levels, that should theoretically guarantee a pain-free postoperative course. This study supports the belief that the dynamic system can be used with the same indications with the rigid in degenerative lumbar spine because it can offer equally good short-term results regarding sagittal spine alignment while simultaneously it has the previously mentioned advantages (avoidance stress shielding etc).

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