Estradiol pulses induce progestin receptors selectively in substance P-immunoreactive neurons in the ventrolateral hypothalamus of female guinea pigs

Low doses of estradiol, administered as pulses, are as effective as higher doses for priming ovariectomized (OVX) guinea pigs to display progesterone-facilitated lordosis. High doses of estradiol, administered by constant-release implants, induce progestin receptors in many substance P-immunoreactive (SP-IR) neurons in the ventrolateral hypothalamus (VLH), a site at which estradiol primes OVX guinea pigs to respond behaviorally to progesterone. To test the hypothesis that behaviorally effective estradiol pulses induce progestin receptors selectively in substance P-containing neurons in the VLH, OVX females received estradiol implants 1 week prior to perfusion, or two pulses of estradiol- 17β, injected 39 and 11 h before perfusion. Colchicine was administered intracerebroventricularly prior to perfusion. No significant differences were observed in the total number of progestin receptor-immunoreactive (PR-IR) or substance P-immunoreactive cells in the VLH and VLH/ventromedial hypothalamus (VMH), respectively, of females receiving the two estradiol treatments. However, the percentage of PR-IR cells in the VLH also immunoreactive for SP was significantly higher in the estradiol pulse-treated (53%), than in the estradiol capsule-implanted animals (36%). These data suggest that behaviorally effective estradiol pulses induce progestin receptors selectively in substance P-containing neurons in the VLH and are consistent with the hypothesis that substance P is involved in progesterone-facilitated lordosis in guinea pigs.     

Functional implications of variation in lumbar vertebral count among hominins

As early as the 1970s, Robinson defined lumbar vertebrae according to their zygapophyseal orientation. He identified six lumbar elements in fossil Sts 14 Australopithecus africanus, one more than is commonly present in modern humans. It is now generally inferred that the modal number of lumbar vertebrae for australopiths and early Homo was six, from which the mode of five in later Homo is derived. The two central questions this study investigates are (1) to what extent do differences in human lumbar vertebral count affect lordotic shape and lumbar function, and (2) what does lumbar number variation imply about lumbar spine function in early hominins? To address these questions, I first outline a biomechanical model of lumbar number effect on lordotic function. I then identify relevant morphological differences in the human modal and extra-modal variants, which I use to test the model. These tests permit evaluation of the human L6 variant as a model for reconstructing early hominin modal number and spine function. Application of the biomechanical model in reconstructing australopith/early Homo lumbar spines highlights shared principles of Euler column strength and sagittal spine flexibility among early and modern hominins. Within modern humans, the extra-modal L6 variant has an extended series of three cranially positioned kyphotic vertebrae and strongly oblique zygapophyseal facets at the last lumbar level. Although they share the same radius and length of lumbar curvature, the L6 variant differs functionally from the L5 mode in its expanded range of sagittal flexion/extension and enhanced resistance to shear. Given the modal number of six lumbar vertebrae in australopiths and early Homo, lumbar spine mobility and strength would have been key properties of vertebral function in early bipeds whose upper and lower body segments were coupled by close approximation of the thorax and iliac crests.     

Progestin receptors in substance P-immunoreactive neurons in the hypothalamus of male guinea pigs after behaviorally effective estradiol pulse treatment

Pulsatile administration of estradiol effectively primes orchidectomized (ORCH) male guinea pigs to display progesterone-facilitated lordosis. In contrast, a single injection of estradiol benzoate (EB) is not behaviorally effective. In ovariectomized female guinea pigs, estradiol pulses induce progestin receptors selectively in substance P neurons in the ventrolateral hypothalamus (VLH), a site at which estradiol primes females to respond behaviorally to progesterone. To test the hypothesis that behaviorally effective estradiol pulses induce progestin receptors selectively in substance P neurons in the VLH in males, ORCH animals received a single injection of EB 40 h before, or two pulses of estradiol-17β, 39 and 11 h before perfusion. Colchicine was administered intracerebroventricularly prior to perfusion. The only difference found between the two estradiol treatment groups was a higher number of progestin receptorimmunoreactive (PR-IR) cells in the rostral VLH of estradiol pulse-treated males. There were no significant differences in the number of PR-IR cells in the mid- or caudal VLH, nor in the number of substance P-immunoreactive (SP-IR) neurons in the VLH/ventromedial hypothalamus (VMH) of animals receiving the two estradiol treatments. Furthermore, the percentage of PR-IR cells in the VLH also immunoreactive for SP did not differ between the estradiol pulse- (22%–25%) and the EB-injected animals (22%–32%). These data do not support the hypothesis that administration of behaviorally effective estradiol pulses, as compared to behaviorally ineffective EB injections, induce progestin receptors selectively in substance P neurons in the VLH of male guinea pigs.     

Oxytocin maintains as well as initiates female sexual behavior: effects of a highly selective oxytocin antagonist

In previous studies, central administration of the oxytocin (OT) antagonist d(CH2)5[Tyr(Me)2, Thr4, Tyr-NH(9)2]OVT (OTA1) blocked receptive and proceptive components of female sexual behavior (FSB) and increased male-directed agonistic behavior when given before progesterone (P) treatment in estradiol-primed female rats but not when given shortly before behavioral testing 4-6 h after P. Because the considerable V(1a) antagonist potency of OTA1 may have contributed to these results, we tested the effects of the far more selective OT antagonist desGly-NH2, d(CH2)5[d-Tyr2, Thr4]OVT (OTA2). In ovariectomized, estradiol benzoate-primed (1 microg x 2 days sc) rats, icv infusion of OTA2 (1 microg) prior to P injection (250 microg sc) significantly suppressed lordosis and hops and darts and trended toward significantly increasing male-directed kicks during testing at 4 and 6 h. Infusion of OTA2 3 h and 40 min after P did not alter behavior at 4 and 6 h after P but significantly decreased lordosis as well as hops and darts and increased male-directed kicks 8-12 h after P. These results provide further evidence that central OT receptor activation shortly after P treatment contributes to the subsequent onset and early expression of FSB and demonstrate, for the first time, that OT receptor activation at later time points also contributes to maintaining FSB. The FSB-stimulating effect of central OT appears to persist for several hours.     

Changes in progesterone metabolites in the hippocampus can modulate open field and forced swim test behavior of proestrous rats

The purpose of these experiments was to test the hypothesis that attenuating the endogenous increase of the 5alpha-reduced progesterone metabolite 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) in the hippocampus will alter anxiety and depression behavior of proestrous rats. In Experiment 1, anxiety (open field) and depression (forced swim test) behavior was compared of rats that should have high (proestrous) and low (diestrous and male rats) endogenous hippocampal 3alpha,5alpha-THP. Proestrous rats exhibited more anxiolytic-like (increased central entries in the open field) and anti-depressant-like (less immobility in the forced swim test) behavior than diestrous or male rats. In Experiments 2 and 3, respectively, systemic and intrahippocampal finasteride, a 5alpha-reductase inhibitor which attenuates progesterone's metabolism to 3alpha,5alpha-THP, versus vehicle administration to proestrous rats was compared for effects on open field and forced swim test behavior. Systemic or intrahippocampal finasteride decreased central entries in the open field and increased immobility in the forced swim tests compared to vehicle administration. In Experiment 4, the effects of systemic and intrahippocampal finasteride vs vehicle administration on hippocampal 3alpha,5alpha-THP of proestrous rats was examined. Finasteride, SC or intrahippocampally, reduced 3alpha,5alpha-THP in the hippocampus compared to vehicle administration. Together these data suggest that variations in 3alpha,5alpha-THP levels in the hippocampus may mitigate proestrous changes in anxiety and depressive behavior of cycling rats.     

Effect of abdominal drawing-in maneuver during hip extension on the muscle onset time of gluteus maximus,hamstring, and lumbar erector spinae in subjects with hyperlordotic lumbar angle

Background

The abdominal drawing-in maneuver (ADIM) is used to prevent abnormal movements of the lumbar spine and pelvis during therapeutic exercises. This study compared the effects of ADIM on the muscle onset time of the hamstring, gluteus maximus, and erector spinae muscles during prone hip extension exercise in subjects with or without hyperlordotic lumbar angle. Forty healthy adults (18 male, 22 female) were recruited for this study.

Methods

The lumbar lordotic angles and pelvic tilt angles of the subjects were measured using the Avaliação postural analysis software. The subjects were divided into two groups: the lumbar hyperlordotic angle (LHLA) and lumbar normal lordotic angle (LNLA) groups. The muscle contraction onset time of the hamstring, gluteus maximus, and erector spinae were assessed using surface electromyography.

Results

During ADIM application, the muscle contraction onset time of the gluteus maximus was significantly increased in the LHLA group compared with the LNLA group.

Conclusions

ADIM application during prone hip extension was more effective for gluteus maximus onset time in the LHLA group. Therefore, ADIM during prone hip extension may be useful for gluteus maximus training in individuals with lumbar hyperlordosis.     

Micro‐anatomical characterization of vertebral curvatures in Senegalese sole Solea senegalensis

The micro‐anatomical changes associated with lordotic and kyphotic vertebral curvatures (VC) in juvenile and adult Senegalese sole Solea senegalensis are described. In addition, it is demonstrated that the tissue and cellular structures of individual vertebrae can be severely affected. Two main conformations were found in deformed juvenile specimens: flattened vertebrae with dorso‐ventral compression and trapezoidal vertebrae forming concave and convex sides under compressive and tensile stresses. Histological analyses revealed the occurrence of an ectopic cartilaginous tissue within the acellular bone, both in juveniles and adults, possibly to cope with altered mechanical stress in deformed vertebrae. The results suggest that the alteration in loading to which curved vertebral columns are subjected might trigger vertebral reshaping and differentiation of cells towards this ectopic tissue. In addition, mesenchymal cells appear to play an important role in its formation. It is here proposed that the acellular bone of S. senegalensis is capable of adaptively responding to altered loading regimes at the structural level by reshaping vertebrae and at the micro‐anatomical level by recruiting chondrocyte‐like cells to areas of altered mechanical stress.     

Effects of intracerebroventricular leptin administration on feeding and sexual behaviors in lean and obese female Zucker rats

Obese Zucker rats (fa/fa) are characterized by inadequate leptin signaling caused by a mutation in the leptin receptor gene. Obese Zucker females are infertile and hyporesponsive to the inductive effects of ovarian hormones on sexual behaviors. Leptin treatment reverses aspects of reproductive dysfunction due to perturbations in energy balance in other animal models. Our first experiment tested the hypothesis that intracerebroventricular (icv) leptin administration would enhance the display of sexual behaviors in obese Zucker females. A second experiment compared lean and obese Zucker females' responses to leptin, during fed and fasted conditions. Ovariectomized (OVX) Zucker rats were implanted with lateral ventricular cannulae. In Experiment 1, fasted, obese females received estradiol benzoate, progesterone, and icv injections of 3, 18, or 36 microg murine leptin or vehicle. Leptin administration reduced food intake, but did not enhance sexual behaviors. In Experiment 2, steroid-replaced, OVX lean and obese females (from a different source than those in Experiment 1) received icv injections of vehicle or 3 or 36 microg leptin under fed and fasted conditions. Leptin treatment reduced food intake and weight gain in the fed, but not the fasted, condition in both genotypes. Sexual receptivity and locomotion were not affected, but icv leptin injections reduced proceptive behaviors in ad libitum-fed rats. These data confirm previous reports that centrally administered leptin decreases food intake and weight gain in obese Zucker rats; results from Experiment 2 suggest that lean and obese females are similarly responsive to these actions of leptin. Contrary to our hypothesis, leptin treatment did not stimulate sexual behaviors; rather, the hormone appears to inhibit the display of sexual proceptivity in ad libitum-fed lean and obese Zucker female rats.     

Cyclic estradiol treatment normalizes body weight and restores physiological patterns of spontaneous feeding and sexual receptivity in ovariectomized rats

Hypothalamic-pituitary-gonadal axis function strongly influences feeding and body weight in cycling females in many species. To test the sufficiency of cyclic variations in plasma estradiol to reproduce normal patterns of spontaneous feeding, food intake, and body weight, ovariectomized Long-Evans rats were subcutaneously injected every fourth day with 2 microg estradiol benzoate or with the oil vehicle alone. Cyclic estradiol treatment completely normalized the trajectory of body weight gain and total food intake through seven treatment cycles. The hyperphagia of ovariectomized rats was expressed as an increase in spontaneous meal size. Meal frequency decreased, but not enough to compensate for the increase in meal size. Estradiol treatment normalized both parameters. In addition, cyclic estradiol treatment produced a further phasic decrease in meal size (and increase in meal frequency) and a decrease in food intake during the second night after injection. This phasic change is similar to the feeding changes occurring during estrus in intact rats. Sexual receptivity was measured during the eighth estradiol treatment cycle, 4 h after injection of 0.5 mg progesterone. Lordosis scores at the time of the treatment cycle modeling estrus were maximal, and scores at the time modeling diestrus were slightly increased over those of rats that did not receive estradiol. Finally, plasma estradiol levels, measured during the ninth treatment cycle, revealed a near-normal cyclic pattern of plasma estradiol levels. These results provide the first demonstration that the induction of a cyclic, near-physiological pattern of plasma estradiol is sufficient to maintain normal levels of body weight, spontaneous feeding patterns, total food intake, and (together with progesterone) sexual receptivity in ovariectomized rats.