Mating behavior: facilitation in the female rat after cortical application of potassium chloride.

Mating behavior in ovariectomized female rats treated with estrogen can be greatly enhanced by subcutaneous injections of progesterone. Application of potassium chloride to the cortex of females previously treated with estrogen can also induce greatly increased sexual receptivity as indicated by the lordosis response. This facilitation of mating behavior by a treatment known to cause functional decortication suggests that mechanisms mediating female mating behavior are under tonic inhibition by an inhibitory system which involves the cerebral cortex.

Enhancement of sexual behavior in female rats by neonatal transplantation of brain tissue from males.

Transplantation of preoptic tissue from male rat neonates into the preoptic area of female littermates increased masculine and feminine sexual behavior in the recipients during adulthood. This suggests that functional connections develop between the transplanted neural tissue and the host brain. A new intraparenchymal brain transplantation technique was used to achieve these results.

Development of hamster circadian rhythms: prenatal entrainment of the pacemaker.

Individual hamster pups were maintained in constant dim light from just prior to birth, and their circadian wheel-running activity rhythms were recorded beginning at 18 days of age. Records of the postweaning free-running activity rhythm were used to determine the phase of a pup's rhythm on the day of weaning. Two groups of pups (LD and DL) were born to mothers that had been entrained before birth to light-dark cycles 12 hr out of phase. Both groups of pups were raised in constant dim light by foster mothers that had been entrained to only one of the prenatal cycles (LD). Thus pups born to mothers from different cycles were exposed to identical rhythmic environments postnatally. Despite the similar postnatal treatment, the two groups of pups showed activity rhythms at weaning with very different phases. The LD pups, born to and raised by LD mothers, were approximately synchronous with one another and with their foster mothers. The DL pups, born to DL mothers, but raised by LD mothers, were not synchronous with one another or with their foster mothers. Half of the DL pups showed phases predicted by their prenatal treatment, but the other half showed scattered phases. The results demonstrate that phase at weaning is affected by prenatal rhythmicity, and suggest that the circadian pacemaker underlying the activity rhythm is already functional and entrained at, or before, birth.

Temporal limits for copulation-induced ovulation in the pentobarbital-blocked proestrous rat.

In two experiments, factors critical to copulation-induced ovulation (CIO) were examined. In Exp I cycling Sprague-Dawley rats were given 25 mg/kg sodium pentobarbital (PB) at 1345 h on proestrus and allowed overnight copulation starting at 1900 (dark onset), 2100, or 2300 h. Only the groups in which copulation began at 1900 or 2100 h displayed ovulation significantly more frequently than PB-treated controls. In Exp II rats received an atrial cannula on diestrus II and 25 mg/kg PB at 1345 h on proestrus. Four blood samples were taken over the course of an hour, starting at 1900 or 2300 h. Controls did not ovulate that night. Rats allowed to copulate for 30 or 60 min starting at 1900 h ovulated and showed elevated plasma LH levels during the period sampled. Copulation at 23 h or cervical probing at 1900 h did not induce LH release or ovulation. There were no differences in the behavior of the males or females during the first 30 min of cohabitation in either experiment; the females were highly receptive. It is concluded that a narrow temporal window exists for CIO, and that temporal changes in induced LH release but not behavior limit CIO.

Effects of ovarian steroids on plasma LH in normal and persistent estrous adult female rats.

The ability of ovarian steroids to influence the release of LH was examined after ovariectomy in regularly cycling adult female rats and two types of anovulatory persistent estrous rats: rats treated with 10 mug of testosterone propionate (TP) shortly after birth, and normal rats housed under constant illumination. Two months after ovariectomy the negative feedback effects of a single injection of 20 mug estradiol benzoate (EB) on plasma LH were measured in these three preparations. Ovariectomized (ovex) normal and TP-treated but not ovex constant light-exposed rats had reduced LH values 6 hr after EB treatment. However, LH levels were reduced by the next day in rats in constant light. Positive feedback was measured in similar EB-primed rats following a second injection of EB or progesterone (P). In ovex normal rats LH values remained low in the morning but increased in the afternoon following the second steroid injection. Ovex EB-primed androgenized rats failed to demonstrate this positive feedback. Similarly, in ovex EB-primed constant light-exposed rats, LH values did not increase after a second EB injection. However, high LH values were observed in the afternoon 6 hr after P administration and again 40 and 50 hr later. These results indicate that the lack of spontaneous ovulation in androgenized rats may be due to the absence of positive feedback to ovarian steroids. Constant light-exposed ovex rats do not respond to the positive feedback action of estrogen and show a different response to P than ovex normal rats, in that a regular diurnal peak in plasma LH is not observed.

Similarity of plasma LH release in androgenized and normal rats following electrochemical stimulation of the basal forebrain.

Because of conflicting data in the literature, the ovulatory response to electrochemical stimulation (ECS) of the medial septal-preoptic complex was measured in pentobarbital-treated normal proestrous and androgenized female rets. Increasing the stimulus strength increases the incidence of ovulation in normal but not in androgenized rats. However, since the ovaries of androgenized rats are relatively insensitive to LH, whereas pituitary responsiveness to LH-releasing factor is normal, the response to ECS was further evaluated in terms of plasma LH. Immunoassayable plasma LH was significantly elevated 30 min after stimulation. Peak LH levels occurred 90 min after stimulation and were returning toward baseline after 120 min. There was no difference in mean plasma LH values in normal and androgenized rats at any time. Stimulation of the diagonal band of Broca, medial septum or medial preoptic area elicited similar plasma LH responses in both groups. These results indicate that the responsiveness of the medial septal-preoptic complex to ECS is not deleteriously affected by neonatal androgen treatment.

Effects of testosterone propionate or dihydrotestosterone propionate on plasma FSH and LH levels in neonatal rats and on sexual differentiation of the brain.

The present study tests the hypothesis that the effects of perinatal androgen administration on the development of the brain are brought about indirectly by a suppression of plasma gonadotropin (GTH) titers. Both castrated male and intact female rats were treated neonatally with 5 alpha-dihydrotestosterone propionate (DHTP) or testosterone propionate (TP) throughout the first ten postnatal days of life and the corresponding effects on neonatal plasma FSH and LH levels and the subsequent ability of the adult to exhibit cyclic GTH release and female sex behavior (lordosis) were determined. In males castrated within 24 h of birth, subcutaneous injections of DHTP (60 or 180 mug per 100 g average body weight) or TP (60 mug/100 g) given on day 2, 4, 6, 8 and 10 reduced plasma levels of FSH and LH as determined by radioimmunoassay 48 h following the first and last injections. However, TP but not DHTP masculinized the development of the regulation of GTH release as mesured by luteinization of subcutaneous ovarian grafts, and also suppressed the ability of adult neonatally castrated male primed with estradiol benzoate and progesterone to display lordosis behavior. In intact females, the same neonatal DHTP and TP injection regime lowered FSH and LH plasma levels following the last injection (day 12), while DHTP lowered LH, but not FSH, following the first injection (day 4). All TP treated females had ovaries devoid of CL by 45 days of age and showed prolonged vaginal cornification. However, DHTP failed to masculinize the pattern of GTH release in females since DHTP-treated females, like oil-treated females, possessed CL(days 45 and 100) and exhibited vaginal cycles (days 80-100). Lordosis quotients of females treated neonatally with DHTP were as high as those of oil-treated females and significantly higher than those of TP-treated females. These results demonstrate that the ability of TP to induce maculine differentiation of the neural regulation of GTH release and female sex behavior does not depend on its ability to depress circulating LH and FSH levels in the neonatal male, or LH levels in the neonatal female rat.

Electrical stimulation of mesencephalic noradrenergic pathway: effects on luteinizing hormone levels in blood of ovariectomized and ovariectomized, steroid-primed rats.

This study examined the effect of electrical stimulation of the dorsal mesencephalic tegmentum (DMT) region on blood LH levels in long term ovariectomized (OVX), pentobarbital-anesthetized rats, with the aim of activating the principal ascending noradrenergic (NE) bundle. In OVX unprimed rats, electrical stimulation (with parameters of 100 Hz, 0.5-msec effective biphasic pulses, 150-200 microA, and 15 sec on/off for up to 1.5 h) of the DMT region inside the ascending NE bundle either completely or partially inhibited the pulsatile pattern of blood LH levels characteristic of OVX animals; stimulation outside the NE bundle was ineffective. Pretreatment of OVX rats with a serotonin synthesis inhibitor, p-chlorophenylalanine (320 mg/kg, ip) 71 h before electrical stimulation of the DMT did not affect the stimulation-induced inhibition of pulsatile LH release. On the other hand, pretreatment of OVX rats with a tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (250 mg/kg, ip) 4.5 h before electrical stimulation of the DMT was effective in preventing the stimulation-induced inhibition of pulsatile LH release, thereby supporting a NE-mediated mechanism. In OVX rats primed with estradiol benzoate alone (5 micrograms/100 g BW for 2 days) or with 50 micrograms estradiol benzoate and 25 mg progesterone, electrical stimulation in the DMT was ineffective in altering the low, nonpulsatile blood levels of LH. The results in OVX unprimed rats suggest that activation of the ascending NE system can inhibit pulsatile LH release, thus indicating a possible functional importance of inhibitory (in addition to well-documented stimulatory) NE synapses in the modulation of LH release.

Estrogen/progesterone treatment in adulthood affects the size of several components of the medial preoptic area in the male rat.

The results of preliminary studies suggested that steroid and/or propylthiouracil (PTU) treatment of adult gonadectomized (Gxd) male rats significantly reduced the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA). Therefore, we designed a study to examine this effect in detail. Groups of adult rats were sham Gxd (intact) or Gxd, then treated with multiple injections of oil (males and females), or estrogen and progesterone (males). Gonadectomized estrogen/progesterone-treated males had a significantly smaller SDN-POA volume, smaller volume of the medial division of the medial preoptic nucleus (MPNm), smaller volume of the anteroventral MPNm (MPNav), and larger volume of the anteroventral periventricular nucleus (AVPv). The volume of the central division of the medial preoptic nucleus (MPNc) or of the suprachiasmatic nucleus was not affected. There were no differences between Gxd estrogen/progesterone-treated males vs the group that received PTU as well, indicating that the PTU treatment was unnecessary. The reduced volume of the SDN-POA was due to a reduced volume of the MPNav and of the portion of the SDN-POA located within the MPNm-exclusive of the MPNav and MPNc. In conclusion, estrogen/progesterone treatment in adulthood caused significant changes in the volume of several medial preoptic structures in two separate groups of Gxd males. Because the steroids produced no significant effects in intact males, testicular hormones appear to "protect" these structures from the effects of the estrogen/progesterone treatment.

Cytoarchitectonic analysis of the SDN-POA of the intact and gonadectomized rat.

The densely staining group of cells referred to as the sexually dimorphic nucleus of the preoptic area (SDN-POA) is greater in volume in the male than in the female rat. Because we and others have reported absolute volumes that have been consistent within individual studies but that vary considerably, we characterized the SDN-POA by describing its morphology with respect to the cytoarchitectonic divisions of the medial preoptic nucleus (MPN) in intact and gonadectomized rats. We report three major findings: the SDN-POA is heterogeneous and is composed of cells belonging to three distinct cytoarchitectonic divisions; the cytoarchitecture of the MPN and its medial and lateral divisions (MPNm and MPNl, respectively) in male rats appear to be influenced by the hormonal status in adulthood; and a small anteroventral division of the MPN (MPNav) is present in males but virtually absent in females. Specifically, the SDN-POA is located within the MPNm, but consists of subcomponents located within the central division of the MPN (MPNc), the MPNav, and part of the MPNm-exclusive of the MPNc and MPNav. The percentage of the total SDN-POA located within the MPNc and MPNav. The percentage of the total SDN-POA located within the MPNc and MPNav was greater in males, and that in the MPNm-exclusive of the MPNc and MPNav was greater in females, indicating that the SDN-POA has a different cytoarchitectonic composition in the two sexes. Gonadectomy produced no significant differences in SDN-POA volume, but the MPN, MPNl, and MPNm were significantly reduced in gonadectomized versus intact males, suggesting an activational effect of testicular hormones on these structures.

Neurogenesis of the sexually dimorphic nucleus of the preoptic area in the rat.

The sexually dimorphic nucleus of the preoptic area (SDN-POA) of Sprague-Dawley rats is larger in volume in the male and hormone-dependent early in postnatal life. In the present study, we compared for each sex the time course of neuroblast proliferation which study, we compared for each sex the time course of neuroblast proliferation which forms SDN-POA or adjacent medial preoptic area (MPOA) neurons. Additionally, we investigated whether there is a temporal gradient of production of neurons in relation to their final position within the SDN-POA. On day 15, 15, 16, 17, or 18 postfertilization (pf) pregnant rats were given a single injection of 3H-thymidine (thy). At 30 postnatally days of age the pups were sacrificed and brain sections were prepared and processed for autoradiography. Three sections of the SDN-POA and an adjacent area just lateral to it in the MPOA were also analyzed. In the MPOA and the SDN-POA the percentage (%) of labeled neurons decreases as the day of injection of thy approaches the end of gestation, but the time period in which neuroblast divisions occurred is markedly different for the SDN-POA as compared to that for the MPOA. DNA synthesis occurs as late as day 18pf for neurons which form the SDN-POA but ceases on day 16pf for those destined for the MPOA. There is a sex difference in neuronal production on both day 14 and 17pf for neurons destined for the SDN-POA. After injection on day 14pf the % labeled neurons is larger in the female than in the male but after injection on day 17pf this is reversed. There are also significant sex differences as well as a temporal gradient associated with the % labeled neurons in the SDN-POA in relation to their final anterior-posterior position. In addition, this study confirms our previous results which justify labeling the SDN-POA a nucleus, since neuronal density in this region in the male and female is significantly greater that that in the surrounding MPOA. These data illustrate that the specific neurons which comprise the SDN-POA in both the male and female are being produced as late as day 18pf, whereas neurons located in the MPOA but not in the SDN-POA have all been born by day 16pf. Neuroblast division which produces the neurons of the SDN-POA may begin earlier and terminate sooner in the female than in the male. These differences in neuronal production may partially account for the sexual dimorphism seen in the volume and neuronal number of the SDN-POA of the adult rat.

Sexual dimorphism of the anterior commissure and massa intermedia of the human brain.

Neuroanatomical sex differences were observed in the midsagittal area of both the anterior commissure and the massa intermedia on analysis of postmortem tissue from 100 age-matched male and female individuals. The anterior commissure, a fiber tract whose axons in primates primarily connect the two temporal lobes, was an average of 12%, or 1.17 mm2 larger in females than in males. The massa intermedia, a structure that crosses the third ventricle between the two thalami, was present in 78% of the females and 68% of the males. Among subjects with a massa intermedia, the structure was an average of 53.3% or 17.5 mm2 larger in females than in males. Inclusive of subjects with and without a massa intermedia, this structure was a mean of 76% or 16.93 mm2 greater in females than in males. These sex differences were present despite the fact that the brains of males were larger than those of females. Since a majority of subjects were adults, it is unknown when sexual differentiation occurred. Anatomical sex differences in structures that connect the two cerebral hemispheres may, in part, underlie functional sex differences in cognitive function and cerebral lateralization.

Sex difference in the bed nucleus of the stria terminalis of the human brain.

A quantitative analysis of the volume of the darkly staining region of the posteromedial bed nucleus of the stria terminalis was performed on the brains of 26 age-matched male and female human subjects. We suggest the term "darkly staining posteromedial" component of the bed nucleus of the stria terminalis (BNST-dspm) to describe this sexually dimorphic region of the human brain. The volume of the BNST-dspm was 2.47 times greater in males than in females. This region in humans appears to correspond to an area of the bed nucleus of the stria terminalis in laboratory animals that exhibits volumetric and neurochemical sexual dimorphisms, concentrates gonadal steroids, and is anatomically connected to several other sexually dimorphic nuclei. Furthermore, the bed nucleus of the stria terminalis is involved in sexually dimorphic functions, including aggressive behavior, sexual behavior, and gonadotropin secretion, which are also influenced by gonadal steroids. Therefore, it is possible that in human beings as well, gonadal hormones influence the sexual dimorphism in the BNST-dspm and that this morphological difference, in part, underlies sexually dimorphic function.

Hormonal modification of the number of total and late-arising neurons in the central part of the medial preoptic nucleus of the rat.

The sexually dimorphic nucleus of the preoptic area (SDN-POA) is larger in volume in males, is responsive to steroids developmentally, and contains a subpopulation of late-arising neurons that can be specifically labeled with 3H-thymidine on embryonic day 18 (E18). The cytoarchitecture of this region has been described, and one component, the central part of the medial preoptic nucleus (MPNc), shows considerable overlap with the SDN-POA. One goal of the present study was to relate the two by determining if testosterone propionate (TP) exposure perinatally increases MPNc volume and neuronal number, and by characterizing the distribution of the late arising neurons of the SDN-POA with respect to the MPNc. A second goal was to determine if these late-arising neurons are a representative, hormone-sensitive population. Finally, TP exposure was delayed past the time of the endogenous testosterone surge in males and after the neurons have become postmitotic, to determine if female brain structure could still be sex-reversed under these conditions. Pregnant rats were injected on E18 with 3H-thymidine. Daily injections of 2.0 mg TP were given to the mothers starting on either E16 or E20 and continued through birth. The pups were injected daily with 100 micrograms TP from birth through postnatal day 10. Control rats, from mothers given oil from E16 until birth, were injected with oil from birth through postnatal day 10. Rats were sacrificed at 30 days of age and their brains processed for autoradiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Demonstration of a sexual dimorphism in the distribution of serotonin-immunoreactive fibers in the medial preoptic nucleus of the rat.

The distribution of serotonergic fibers in the medial preoptic nucleus (MPN) and adjacent areas was evaluated with an indirect immunohistochemical method in the normal adult male and female albino rat. Sections through the MPN were processed for immunofluorescence with an anti-serum directed toward serotonin and were counterstained with the fluorescent Nissl stain ethidium bromide. The distribution of serotonin-immunoreactive fibers in the MPN was correlated with cytoarchitectonic features of the nucleus. On the basis of the results, we have subdivided the MPN into three parts: a medial cell-dense part ( MPNm ), a lateral cell-sparse part ( MPNl ), and a central very cell-dense part ( MPNc ) that is embedded in the medial part. The MPNc corresponds to the sexually dimorphic nucleus of the preoptic area identified by Gorski et al. ('80). A marked sexual dimorphism was found in the relative size of each part of the MPN. In the male, the volumes of the cell-dense MPNm and MPNc appear to be notably larger, while in the female more than half of the nucleus is occupied by the cell-sparse lateral part. The MPN as a whole appears to be slightly larger in the male. Each subdivision contains a characteristic pattern of serotonin-immunoreactive fibers. In each sex, the MPN is surrounded by a low to medium density of serotonin-stained fibers, while the MPNl is filled with a dense plexus of varicose immunoreactive fibers. In contrast, the MPNm contains a low density of stained fibers, and the MPNc is virtually devoid of serotonin-stained fibers. Since both the MPNm and the MPNc are larger in the male, a correspondingly larger region of very low serotonin-stained fiber density is found in the male. It appears then that the MPN is a sexually dimorphic complex composed of at least three cytoarchitectonically distinct subdivisions, each of which contains a characteristic density of serotonin-immunoreactive fibers.

Neurotransmitter specificity of cells and fibers in the medial preoptic nucleus: an immunohistochemical study in the rat.

The medial preoptic nucleus (MPN) is a sexually dimorphic complex with three major subdivisions. The cell-dense central (MPNc) and medial (MPNm) subdivisions are larger in male rats, while the cell-sparse lateral subdivision (MPNl) occupies a majority of the nucleus in females. In the present study we evaluated the distribution of possible monoaminergic and peptidergic cells and fibers within the MPN, as well as in adjacent regions of the medial preoptic area of the adult male rat. For this, we used an indirect immunohistochemical method with antisera to serotonin (5HT), dopamine beta-hydroxylase (DBH), tyrosine hydroxylase (TH), neuropeptide Y (NPY), cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), substance P (SP), neurotensin (NT), corticotropin-releasing factor (CRF), luteotropin-releasing hormone (LRH), somatostatin (SS), thyrotropin-releasing hormone (TRH), oxytocin (OXY), vasopressin (VAS), adrenocorticotropic hormone (1-24; ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), leucine-enkephalin (L-ENK), and calcitonin gene-related peptide (CGRP). The results suggest that cell bodies and/or fibers crossreacting with all of these putative neurotransmitters are differentially distributed within the MPN. Within the MPNm, the densest plexuses of fibers were stained with antisera to SP and NPY, while moderate densities of fibers were stained with anti-DBH, SS, CCK, CGRP, ACTH, and alpha-MSH, and only a few fibers were stained with anti-5HT, TH, NT, VAS, and L-ENK. Moderate numbers of SP- and L-ENK-immunoreactive cell bodies, and a few SS-, NT-, CRF-, and TRH-stained cell bodies were also found within the MPNm. The MPNc contained a dense plexus of CCK-immunoreactive fibers, as well as a few CRF-immunoreactive fibers. Both fiber types were localized almost exclusively to this subdivision, while most of the others studied here appeared to avoid it selectively. This suggests that there are relatively few inputs to the MPNc, and that they tend to avoid other parts of the nucleus, although moderate densities of DBH- and NPY-immunoreactive fibers were found in both the MPNm and MPNc. The MPNc contained several CCK-immunoreactive cell bodies as well as a moderate number of TRH-stained cell bodies. Both cell types were nearly completely localized to the MPNc. The major inputs to the MPNl studied here appear to be stained with antisera to 5HT and L-ENK, although moderate numbers of NT- and CRF- immunoreactive fibers were also found in this part of the nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Evidence for the existence of a sexually dimorphic nucleus in the preoptic area of the rat.

The volume of an intensely staining component of the preoptic area of the male rat is markedly larger than that of the female. Moreover, its volume in both sexes is altered by perinatal hormone exposure consistent with the view that this brain region undergoes hormone dependent sexual differentiation. The present study was carried out to determine if this sexually dimorphic area of the brain has a greater cell density than that of the surround, and if a unique population or distribution of cells, either within one sex or between males and females, characterized this region. A single coronal paraffin section (10 micrometer) through the approximate center of this sexually dimorphic area in four adult gonadectomized rats of each sex was evaluated systematically. Each cell was labelled as being inside or outside of the sexually dimorphic area. In addition to cell density per unit area the following parameters were evaluated through a closed-circuit video system: cell size, staining intensity, shape, and the presence of processes and of a nucleolus. The presence of a nucleolus was further used to identify neurons within the total population of almost 5000 cells that was evaluated. In both sexes, the sexually dimorphic area was characterized by a significantly increased cell density per unit area compared to that of the surround. On this basis, the term, the Sexually Dimorphic Nucleus of the Preoptic Area (SDN-POA) is proposed, for this region. Moreover, the SDN-POA of the male was characterized by increased neuronal density per unit area. The SDN-POA in the male was also found to contain larger cells and neurons, as determined by direct measurement of their greatest diameter, as well as a greater percentage of cells and neurons rated large on a three-point scale (small, medium, and large). No consistent differences in frequency distribution by stain intensity, shape, or the presence of cell processes were found to characterize the SDN-POA or contribute to the sexual dimorphism. It is concluded that the marked sex difference in the volume of the SDN-POA is due principally to an increase in the male of the total area of higher cell and neuronal density. However, the present results do not eliminate the possibility that more subtle differences in neuronal characteristics may exist in the SDN-POA.

Homogeneity of intracellular electrophysiological properties in different neuronal subtypes in medial preoptic slices containing the sexually dimorphic nucleus of the rat.

The sexually dimorphic nucleus of the preoptic area (SDN-POA) is larger in male than in female rats, the male phenotype requiring the presence of circulating androgens perinatally. These experiments investigated the intracellular electrophysiology and morphology of SDN-POA neurons and compared these properties with those of other medial preoptic area (MPOA) neurons. Biocytin-injected cells in the SDN-POA either had one or two primary dendrites, or they had multipolar dendritic arrays; dendrites were aspiny or sparsely spiny and displayed limited branching. Neurons in other parts of the MPOA were similar morphologically. Regardless of morphology, neurons situated in either the SDN-POA or surrounding MPOA had low-threshold potentials and linear or nearly linear current-voltage relations. In most (73%) cells, stimulation of the dorsal preoptic region evoked a fast excitatory postsynaptic potential followed by a fast inhibitory postsynaptic potential (IPSP). Bicuculline blocked the fast IPSPs, which reversed near the Cl2 equilibrium potential (-71 +/- 5 mV), indicating their mediation by gamma-aminobutyric acid (GABA)A receptors. Neurons in the SDN-POA have electrophysiological properties similar to those of other medial preoptic cells. When compared with the hypothalamic paraventricular nucleus, the MPOA appears relatively homogeneous electrophysiologically. This is despite the morphological variability within this population of neurons and heterogeneities that are also apparent at other levels of analysis. Finally, GABA-mediated, inhibitory synaptic contacts are widespread among medial preoptic neurons, consistent with indications from earlier reports that GABA provides a link in the feedback actions of gonadal steroids on the release of gonadotropic hormones.

Sexual differentiation of the brain: a model for drug-induced alterations of the reproductive system.

The process of the sexual differentiation of the brain represents a valuable model system for the study of the chemical modification of the mammalian brain. Although there are numerous functional and structural sex differences in the adult brain, these are imposed on an essentially feminine or bipotential brain by testicular hormones during a critical phase of perinatal development in the rat. It is suggested that a relatively marked structural sex difference in the rat brain, the sexually dimorphic nucleus of the preoptic area (SDN-POA), is a morphological signature of the permanent or organizational action of estradiol derived from the aromatization of testicular testosterone. The SDN-POA of the male rat is severalfold larger in volume and is composed of more neurons than that of the female. The observation that the mitotic formation of the neurons of the SDN-POA is specifically prolonged has enabled us to identify the time course and pathway of neuronal migration into the nucleus. Study of the development of the SDN-POA suggests that estradiol in the male increases the number of neurons which survive a phase of neuronal death by exerting a neurite growth promoting action and/or a direct neuronotrophic action. It may not be possible to extrapolate this trophic effect of estradiol to all other structural sex differences since in the anteroventral periventricular nucleus, steroid exposure reduces the number of immunohistochemically defined dopaminergic neurons. Finally, although it is clear that gonadal hormones have dramatic permanent effects on the brain during perinatal development, even after puberty and in adulthood gonadal steroids can alter neuronal structure and, perhaps as a corollary to this, have permanent effects on reproductive function. For example, in the lightly androgenized rat which exhibits the delayed anovulation syndrome, exposure to estrogen prepubertally delays the onset of ovulatory failure, whereas estrogen exposure peri- or post-pubertally has an inhibitory effect on ovulation. Although the brain may be most sensitive to gonadal hormones or exogenous chemical factors during perinatal development, such sensitivity does not appear limited to this period.