Estradiol-associated variation in responses of rostral medullary neurons to somatovisceral stimulation

The lordosis posture and cervix stimulation during copulation are important reproductive events involving complex neural circuitries that are under hormonal influence. An important component of this circuitry, neurons within the medullary reticular formation (MRF), was examined in the present study using electrophysiological techniques. Single unit extracellular recordings were performed in the MRF of 27 urethane-anesthetized female rats. Using bilateral electrical stimulation of the dorsal nerve of the clitoris as the search stimulus, a detailed examination of the somatovisceral convergent responses of 585 individual MRF neurons was made. A total of 7 different groups of cycling and ovariectomized/hormone-supplemented rats were examined and their neuronal response properties to mechanical stimulation of various pelvic organs (cervix pressure, vaginal distension, colon distension) compared. The results indicate the existence of complex response properties as well as several variations in MRF response characteristics that are hormone-dependent. Specifically, estradiol is associated with hyposensitivity to cervix pressure and hypersensitivity to stroking the face. These opposing effects of estradiol in the same subset of neurons likely relate to lordosis behavior which can be either disrupted or elicited, depending on the area being stimulated (upper versus lower parts of the body, respectively).     

Membrane estradiol signaling in the brain

While the physiology of membrane-initiated estradiol signaling in the nervous system has remained elusive, a great deal of progress has been made toward understanding the activation of cell signaling. Membrane-initiated estradiol signaling activates G proteins and their downstream cascades, but the identity of membrane receptors and the proximal signaling mechanism(s) have been more difficult to elucidate. Mounting evidence suggests that classical intracellular estrogen receptor-α (ERα) and ERβ are trafficked to the membrane to mediate estradiol cell signaling. Moreover, an interaction of membrane ERα and ERβ with metabotropic glutamate receptors has been identified that explains the pleomorphic actions of membrane-initiated estradiol signaling. This review focuses on the mechanism of actions initiated by membrane estradiol receptors and discusses the role of scaffold proteins and signaling cascades involved in the regulation of nociception, sexual receptivity and the synthesis of neuroprogesterone, an important component in the central nervous system signaling.     

A computer-based measure of irregularity in vertebral alignment is a BMD-independent predictor of fracture risk in postmenopausal women

SUMMARY: Prevalent fracture and BMD are core elements of fracture prediction. In this control study case, we demonstrate that a simple computer-based estimation of local irregularities in the alignment of the lumbar vertebrae independently contributes to the fracture risk, thus supplementing current diagnostic tools. INTRODUCTION: We tested the hypothesis that degree of lordosis and/or irregularity in the alignment of lumbar vertebrae could be contributors to the risk of fragility fractures. METHODS: This was a case-control analysis including 144 elderly women; 108 maintaining skeletal integrity, whereas 36 sustaining a lumbar vertebral fracture during a 7.5-year observation period. The two groups of women were carefully matched for age, BMI, spine BMD and numerous classic risk factors. Lateral X-rays of the lumbar spine were digitized and the four corner points of endplates on each vertebra from Th12 to L5 were annotated. The degree of lordosis and irregularity of vertebral alignment was assessed by image analysis software. RESULTS: Degree of lordosis was not predictive for fractures. In contrast, irregularity was significantly higher in those who later sustained a fracture (1.6 x 10(-2)vs. 2.0 x 10(-3) cm(-1), p < 0.001), and further increased upon a sustained fracture (2.8 x 10(-2) cm(-1), p < 0.001), but was unchanged in controls (1.6 x 10(-2) cm(-1)). The predictive value of irregularity was independent of classic risk factors of fractures, including BMD (p < 0.01). CONCLUSION: Our results suggest that the herein introduced simple measure of irregularities in vertebral alignment could provide useful supplement to the currently used diagnostic tools of fracture prediction in elderly women.     

Dihydrotestosterone-induced inhibition of lordosis in estrogen-primed ovariectomized rats following 6-hydroxydopamine or electrolytic septal lesions

The dose-dependent inhibition of lordosis by 5α-dihydrotestosterone propionate in ovariectomized female rats treated concurrently with estradiol benzoate was attenuated neither by intracranial 6-hydroxydopamine injections which reduced dopamine concentrations by approximately 70% in septum or 75% in both septum and n. accumbens septi nor by electrolytic destruction of the lateral or medial septal nuclei or of both septal nuclei. These results suggest that the inhibitory effect of dihydrotestosterone on estrogen-induced lordosis does not critically depend on the mesolimbic dopaminergic innervation of the forebrain or on the septal nuclei.     

Neuronal activity in female rat preoptic area associated with sexually motivated behavior

Single unit activities were recorded from 31 neurons in the preoptic area (POA) of female rats engaging in sexual interactions. Concurrent videotape recordings were used to establish a relationship between neuronal activity and particular behavioral events. In 14 of the 31 neurons, the firing rate changed in association with bouts of sexual activity. The remaining 17 fired with more variability regardless of episodes of sexual interactions. Peri-event histograms identified four types of neurons: type 1 (n=4) increased their firing rate when the female rats initiated proceptive behavior; type 2 (n=4) showed a brief activation when the male mounted; type 3 (n=4) fired in response to intromission, and type 4 (n=2) were inhibited prior to and throughout the display of lordosis reflex. Type 1 neurons fired at significantly higher rates during the solicitatory period, from the initiation of solicitatory locomotion to the male mounts. Their activity was suppressed when the males mounted successfully with intromission. Types 1–3 neurons were recorded from the transitional region between the medial and lateral POAs. Type 4 neurons were located more medially in the medial POA. Systemic injection of pimozide, a dopamine receptor blocker, diminished firing in type 1 neurons and abolished proceptivity. The firing pattern in type 1 neurons appeared to embody the motivational state of the animal with an implication for a consummatory value of penile intromission. Visceral or somatosensory inputs may be responsible for short bursts in types 2 and 3 neurons. Type 4 neurons behaved exactly as if they inhibit the execution of the lordosis reflex. The results showed separate sets of POA neurons each specifically associated with proceptive and receptive components of female rat sexual behavior.     

Effects of dexamethasone, corticosterone, and ACTH on lordosis in ovariectomized and adrenalectomized-ovariectomized rats

The involvement of the pituitary-adrenocortical axis in the control of the lordosis reflex was investigated; In Experiment 1, estrogen-primed ovariectomized (ovx) and adrenalectomized-ovariectomized (adx-ovx) females were treated chronically with dexamethasone, a compound blocking ACTH release from the pituitary. Dexamethasone inhibited lordosis, effectively blocking an adrenalectomy-induced facilitation of the reflex. In Experiment 2, corticosterone was similarly administered chronically; this compound also inhibited lordosis in adx-ovx females. In Experiment 3, acute peripheral administration of synthetic ACTH caused a marked increase in lordosis in ovx females. The results suggest that in the adrenally intact animal, ACTH may exert its effect through adrenal steroids. An acute elevation of adrenal steroids may increase lordosis, whereas a chronic elevation may decrease it.     

Responses of medullary reticulospinal and other reticular neurons to somatosensory and brainstem stimulation in anesthetized or freely-moving ovariectomized rats with or without estrogen treatment

Summary The medial medullary reticular formation (mMRF) is probably involved in controlling lordosis, a feminine mating reflex which requires both estrogen priming and appropriate somatosensory input(s). We have recorded single-unit activity of antidromically identified reticulospinal (RS) and unidentified (UI) neurons in mMRF of ovariectomized rats with or without estrogen treatment to investigate neurohormonal mechanisms regulating lordosis. The units were recorded in both acute and chronic preparations, the latter involving implanted floating wire electrodes to allow the influence of estrogen on a particular unit to be followed for several days.A substantial number of RS and UI units in both acute and chronic preparations were either excited or inhibited by a lordosis-eliciting somatosensory stimulation, indicating that the lordosis-eliciting sensory inputs did reach mMRF. The majority of these units responded promptly to the stimulation, and could participate in triggering the short-latency lordosis reflex. Electrical stimulation of several brainstem locations revealed that there was an extensive and specific convergence on mMRF neurons between inputs from the lordosis-eliciting stimulation and mesencephalic central gray, which has been shown to relay lordosis-inducing estrogen influence from hypothalamus to lower brainstem. Therefore, mMRF neurons can receive both the estrogen influence and the lordosis-eliciting inputs and integrate them. Although no apparent estrogen influence was detected in chronic preparations, statistical comparisons of results from acute preparations with or without estrogen treatment suggest that estrogen can increase the proportion of the neurons excited by the lordosis-eliciting stimulation and facilitate neuronal excitability. Both effects are consistent with the prevailing notion that the net lordosis-inducing influence of estrogen is facilitatory, and they may be mechanisms for making lordosis elicitable.Supported by NIH grant HD 05751     

Progesterone: examination of its postulated inhibitory actions on lordosis during the rat estrous cycle.

Three experiments tested whether the inhibitory effects of progesterone could be of physiological significance in regulating the duration of behavioral estrus in female rats. In animals displaying 5 day estrous cycles, a second period of sexual receptivity, one day following the occurrence of spontaneous estrus, could be induced by exogenous hormone administration, regardless of whether the ovaries were intact or were removed during the period over which the exogenous hormones were acting. In a second experiment, acute ovariectomy at various times during the progesterone surge acted only to degrade the quality of receptive behavior subsequently observed, never to enhance it by removing a postulated inhibitory influence. In the final experiment there was some suggestion that progesterone's facilitating effect on lordosis during the later portions of spontaneous estrus were attenuated by prior exposure to ovarian secretions during the early period of behavioral estrus. Our results are consistent with the hypothesis that the duration of receptive behavior under physiological conditions is not primarily regulated by inhibitory actions of progesterone, but rather by the quantity and duration of estrogen secretions during the conditioning period.     

Intracerebral implantation of the anti-estrogen CN-69, 725-27: Effects on female sexual behavior in rats

Ovariectomized adult female rats were stereotaxically implanted with double walled cannulas (22 ga outer and 27 ga inner) and tested for sexual receptivity (lordosis behavior) following SC estradiol benzoate and progesterone priming. Implantation of the anti-estrogen CN-69,725-27 (c. 6.5 μg) immediately after the first of 3 daily estrogen injections produced a dramatic inhibition of sexual receptivity when these implants were placed in the preoptic and anterior hypothalamic areas. CN-69,725-27 implants had no effect on receptivity when implanted in the middle hypothalamus, mesencephalon or frontal cortex. All inhibitory effects of the anti-estrogen were reversible within one day after removal of the CN-69,725-27 cannula from the brain.