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 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 14, 15, 16, 17, or 18 postfertilization (pf) pregnant rats were given a single injection of ³H-thymidine (*thy). At 30 postnatal 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 wer 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 than 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.     

Ontogeny of opiate receptors in the rat medial preoptic area: Critical periods in regional development

Opiate receptor labeling was examined throughout the early postnatal period using autoradiography to localize and quantify [³H]naloxone binding to μ-type opiate receptors in the medial preoptic area (MPOA). This region begins to exhibit sexual dimorphism of volume and dendritic growth shortly after birth. A distinct concentration of opiate receptor labeling appears on postnatal day 3 in females: this labeling is directly associated with the sexually dimorphic nucleus of the preoptic area (SDN-POA). SDN-POA labeling becomes denser through postnatal day 10 in females and the densely labeled area increases in size to encompass and surround the SDN-POA. These changes in opiate receptor labeling occur only in females, since males show relatively uniform labeling across the region throughout the early postnatal period.The critical time of formation of dense MPOA opiate receptor labeling may be related to endogenous MPOA opioid function and to the critical period of dendritic growth of SDN-POA neurons. The timing of these critical periods and their focus in the SDN-POA are coincident. The possible role of MPOA opiate receptors in modulating growth of MPOA neurons is discussed.     

The interstitial nuclei of the human anterior hypothalamus: an investigation of sexual variation in volume and cell size, number and density

The four interstitial nuclei of the anterior hypothalamus (INAH) have been considered as candidate human nuclei for homology with the much studied sexually dimorphic nucleus of the preoptic area of the rat. Assessment of the INAH for sexual dimorphism has produced discrepant results. This study reports the first systematic examination of all four INAH in the human for sexual variation in volume, neuronal number and neuronal size. Serial Nissl-stained coronal sections through the medial preoptic area and anterior hypothalamus were examined from 18 males and 20 females who died between the ages of 17 and 65 without evidence of hypothalamic pathology or infection with the human immunodeficiency virus. A computer-assisted image-analysis system and commercial stereology software package were employed to assess total volume, neuronal number and mean neuronal size for each INAH. INAH3 occupied a significantly greater volume and contained significantly more neurons in males than in females. No sex differences in volume were detected for any of the other INAH. No sexual variation in neuronal size or packing density was observed in any nucleus. The present data corroborate two previous reports of sexual dimorphism of INAH3 but provide no support for previous reports of sexual variation in other INAH.     

Simultaneous catecholamine histofluorescence and thymidine autoradiography of the sexually dimorphic nucleus of the preoptic area in the rat

The sexually dimorphic nucleus of the preoptic area (SDN-POA) in the rat represents a morphological substrate in which the influence of gonadal hormones on the process of sexual differentiation of the brain can be seen. Since the medial preoptic area (MPO) is a region rich in catecholamine (CA) terminals, it is possible that catecholamines may play a role either in the differentiation of the perinatal SDN-POA or in the function of this nucleus in the adult. It is not known whether catecholamine terminals exist within the SDN-POA or whether they can directly influence the activity of SDN-POA neurons. The present study was conducted to determine the extent to which catecholamines innervate this nucleus and further to elucidate the possibility of a potential sexual dimorphism in the innervation pattern. In order to determine which of the neurons in the MPO are within the SDN-POA we have utilized the fact that the SDN-POA has a prolonged period of neurogenesis in comparison to other neurons of the MPO. Thus, tritiated thymidine-labeled neurons can be used as a detection criterion for the SDN-POA. To conduct this experiment, timed pregnant Sprague-Dawley females were given a single injection of [3H]thymidine on Day 18 of gestation. Pups were killed as adults and prepared for fluorescence histochemistry of monoamines. Sections adjacent to those examined for catecholamine fluorescence were treated for autoradiographic localization of [3H]thymidine. Fluorescence innervation patterns were plotted within the boundaries of the nucleus following its identification from Nissl sections as well as from adjacent autoradiograms simultaneously viewed in a comparator bridge microscope with dark-field illumination.(ABSTRACT TRUNCATED AT 250 WORDS)     

The sex hormone-dependent development of opiate receptors in the rat medial preoptic area

The opiate receptor content of the sexually dimorphic medial preoptic area (MPOA) was examined in newborn and 5-day-old (D6) male and female rats. A significant increase of [³H]naloxone binding was observed in and around the sexually dimorphic nucleus of the preoptic area (SDN-POA) in D6 female rats, relative to newborn females. Opiate receptor labeling did not increase over this period in males, nor was labeling different between males and females at birth. This dramatic alteration of MPOA opiate receptor content was observed to occur in either sex in the absence of testosterone postnatally; that is, neonatally-castrated males exhibited the same increase of labeling by D6 as did normal females. Conversely, daily postnatal testosterone treatment of females from birth to D6 resulted in the development of male-like MPOA opiate receptor pattern. The sex hormone-dependence of MPOA opiate receptor development is discussed in relation to the sex hormone-dependent ontogeny of SDN-POA structure. The overlap of critical periods for the development of these structural and chemical sexual dimorphisms suggests a role for endogenous opioids in modulating MPOA development.     

Comparative neuroanatomy of the sexually dimorphic hypothalamus in monogamous and polygamous voles

In the present work we evaluated the degree of sexual dimorphism in two cell groups of the medial preoptic-anterior hypothalamus (MPOA-AH) in monogamous and polygamous voles. Quantitative determinations were made of volume, cell number, and cell density for the anteroventral-periventricular nucleus (AVPV) and the sexually dimorphic nucleus of the preoptic area (SDN-POA). Polygamous montane voles (Microtus montanus) had a greater degree of sexual dimorphism in both cell groups than did monogamous prairie voles (M. ochrogaster). Most notable was the complete absence of the AVPV in male montane voles; male montane voles also had a significantly larger SDN-POA volume than did females. The only sexual dimorphism in prairie voles was a greater cell density in the female AVPV. In addition, prairie voles had larger relative brain size than did montane voles. Comparative behavioral studies have revealed a correlation between the degree of sexual dimorphism in external morphology and mating system, i.e., polygamous species display greater levels of dimorphism than do monogamous species. The present results indicate that the effects of sexual selection can also be seen in those brain regions, like the hypothalamus, that underlie social and reproductive behavior. Moreover, these results support the hypothesis that neuroanatomic dimorphisms in the MPOA-AH may be related to sex differences in behavior.     

Gonadal Steroid Action and Brain Sex Differentiation in the Rat

Gonadal steroids that establish sexually dimorphic characteristics of brain morphology and physiology act at a particular stage of ontogeny. Testosterone secreted by the testes during late gestational and neonatal periods causes significant brain sexual dimorphism in the rat. This results in both sex-specific behaviour and endocrinology in adults. Sexual differentiation may be due to neurogenesis, migration or survival. Each mechanism appears to be uniquely regulated in a site-specific manner. Thus, the volume of an aggregate of neurones in the rat medial preoptic area (POA), termed the sexually dimorphic nucleus of the POA (SDN-POA), is larger in males than in females. The anteroventral periventricular nucleus (AVPV) is packed with neurones containing oestrogen receptor (ER)β in female rats but, in males, ERβ-positive neurones scatter into the more lateral portion of the POA. POA neurones are born up to embryonic days 16–17 and not after parturition. Therefore, neurogenesis is unlikely to contribute to the larger SDN-POA in males. DNA microarray analysis for oestrogen-responsive genes and western blotting demonstrated site-specific regulation of apoptosis- and migration-related genes in the SDN-POA and AVPV.     

Pre- and postnatal influence of testosterone propionate and diethylstilbestrol on differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats

The volume of the sexually dimorphic nucleus in the preoptic area (SDN-POA) of the rat brain is several fold larger in males than in females. When female rats were treated pre- and postnatally with testosterone propionate (TP) or with diethylstilbestrol (DES) they became anovulatory and their SDN-POA developed equivalent in size to that of normal males. Identical treatment of male rats resulted in deficient testicular development, but had no influence on SDN-POA volume. The results indicate that the gross morphological sex difference in SDN-POA volume can exclusively be controlled by the hormonal environment during the critical period of sexual brain differentiation, and that non-steroidal estrogens are just as effective as convertible androgens in stimulating SDN-POA differentiation.     

Sex Differences and the Roles of Sex Steroids in Apoptosis of Sexually Dimorphic Nuclei of the Preoptic Area in Postnatal Rats

The brain contains several sexually dimorphic nuclei that exhibit sex differences with respect to cell number. It is likely that the control of cell number by apoptotic cell death in the developing brain contributes to creating sex differences in cell number in sexually dimorphic nuclei, although the mechanisms responsible for this have not been determined completely. The milieu of sex steroids in the developing brain affects sexual differentiation in the brain. The preoptic region of rats has two sexually dimorphic nuclei. The sexually dimorphic nucleus of the preoptic area (SDN-POA) has more neurones in males, whereas the anteroventral periventricular nucleus (AVPV) has a higher cell density in females. Sex differences in apoptotic cell number arise in the SDN-POA and AVPV of rats in the early postnatal period, and an inverse correlation exists between sex differences in apoptotic cell number and the number of living cells in the mature period. The SDN-POA of postnatal male rats exhibits a higher expression of anti-apoptotic Bcl-2 and lower expression of pro-apoptotic Bax compared to that in females and, as a potential result, apoptotic cell death via caspase-3 activation more frequently occurs in the SDN-POA of females. The patterns of expression of Bcl-2 and Bax in the SDN-POA of postnatal female rats are changed to male-typical ones by treatment with oestrogen, which is normally synthesised from testicular androgen and affects the developing brain in males. In the AVPV of postnatal rats, apoptotic regulation also differs between the sexes, although Bcl-2 expression is increased and Bax expression and caspase-3 activity are decreased in females. The mechanisms of apoptosis possibly contributing to the creation of sex differences in cell number and the roles of sex steroids in apoptosis are discussed.     

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 m?m) 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.     

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.     

Preoptic lesions increase the display of lordosis by male rats

Male rats do not normally show feminine patterns of sexual behavior even when injected with the ovarian hormones estrogen and progesterone. We find that brain lesions which damage the preoptic-anterior hypothalamic continuum augment the display of lordosis in hormone-treated male rats. The most effectively feminizing brain lesions are ones which bilaterally destroy a substantial portion of the medial preoptic area encompassing the sexually dimorphic nucleus of the preoptic area (SDN-POA). Males with particularly large preoptic lesions are receptive following estrogen treatment and show a progesterone facilitation of receptivity. In this respect, they cannot be behaviorally distinguished from females. Thus, axons originating in and/or passing through the preoptic area apparently inhibit the display of feminine sexual behaviors in males. Preoptic development and lordosis are each predictably affected by perinatal stimulation by testicular hormones, and hormone-stimulated preoptic development may form the neurological basis for some of the defeminizing effects of perinatal hormonal exposure. Our results raise the possibility that the site of this behavioral defeminization is the SDN-POA.     

Sex differences in dendritic patterns in hamster preoptic area

Sexual dimorphism is described in the dendritic field pattern of Golgi-stained neurons from the dorsomedial preoptic area of adult golden hamsters (Mesocricetus auratus). Data were obtained through a mathematical reconstruction of dendritic densities of neurons sampled from this area in males and females. Males tended to have a central concentration, while females showed an irregular dendritic density distribution with concentrations dorsolateral, ventral and medial to the area of highest dendritic density in the males. These results suggest sex differences in the afferent inputs to neurons in the dorsomedial preoptic area which may be related to functional sexual dimorphism in physiology and behavior.     

A comparison of hypothalami of rats and mice: lack of gross sexual dimorphism in the mouse

Anterior hypothalami from 10 male and 10 female CBA/j type mice were sectioned serially and examined histologically for possible sexual dimorphisms in appearance and size of neuronal aggregations. Measurements of volumes of suprachiasmatic nuclei and an adjacent cell aggregation, designated as the medial portion of the anterior hypothalamic nucleus (AHm) and similar in appearance and position to the sexually dimorphic nucleus of the rat, were made. In contrast to known sexual dimorphism present in the rat, no sex differences in volumes of mouse hypothalamic structures were found. This lack of gross sexual dimorphism in the mouse could be explained by (a) insensitivity of dividing and developing AHm neurons to androgens, or by (b) a possible influence of androgens upon overall AHm morphology in both sexes, due to transfer of androgens from males to females in utero.     

Ontogeny of the sexually dimorphic nucleus of the preoptic area

An area of increased cell density in the medial preoptic area of the adult rat brain which is markedly larger in volume in the male has been named the Sexually Dimorphic Nucleus of the Preoptic Area (SDN-POA). It has been further shown that the presence of the testes or exogenous androgen during the first week of postnatal life significantly increases the volume of the SDN-POA in the brain of the adult. The present study was conducted to describe the time course of the prenatal and postnatal development of the SDN-POA in the intact male and female rat. Sprague-Dawley females were housed with males on proestrus. The presence of sperm in the vaginal smear on estrus was used to define day 1 of gestation. Male and female prenatal and postnatal pups were sacrificed and perfused with 10% neutral formalin on days 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, and 32 postfertilization. Following histological sectioning at 60 m?m and staining with thionin, three investigators independently drew the boundaries of the SDN-POA on successive sections, using a microprojector at a magnification of 43.5. A fourth investigator averaged the three drawings; from this average, the nuclear volume was determined with a calibrated planimeter. All drawings and measurements were performed without knowledge of age or sex since the brains were coded according to a random number generator. The volume of the SDN-POA was found to be significantly larger in males than in females on days 23, and 25 through 32. Moreover, the volume of the SDN-POA increased significantly with age in the male, but there was no change in SDN-POA volume in the female. In order to test the specificity of the sexual dimorphism of the SDN-POA, five different linear measurements were taken of brain size. There was a significant increase in these parameters in both sexes with increasing age; however, there was no significant sex difference found. Thus, the sex difference in volume of the SDN-POA cannot be accounted for by sex differences or age-related changes in brain size per se. These data suggest that the development of the SDN-POA (as measured by volume) is itself sexually dimorphic. There are dramatic increases in the male, but not in the female, during a time-period which is known to be critical for sexual differentiation of the brain.     

Neuronal aromatase expression in preoptic,strial, and amygdaloid regions during late prenatal and early postnatal development in the rat

Brain aromatase has been considered to be an important clue in elucidating the actions of androgen on brain sexual differentiation. Using highly specific anti-P450arom antiserum, the regional and subcellular distributions were immunohistochemically evaluated in the preoptic, strial, and amygdaloid regions of developing rat brains. Aromatase-immunoreactive (AROM-I) neurons were classified into three groups. The first, in which immunostaining occurs only during certain pre- or neonatal days (E16–P2), included the anterior medial preoptic nucleus, the periventricular preoptic nucleus, neurons associated with the strial part of the preoptic area, and the rostral portion of the medial preoptic nucleus. The second is a striking AROM-I cell group in the “medial preopticoamygdaloid neuronal arc,” which extends from the medial preoptic nucleus to the principal nucleus of the bed nucleus of the stria terminals and the posterodorsal part of the medial amygdaloid nucleus. The AROM-I neurons appeared by E16, reaching a peak in staining intensity between E18 and P2 and diminishing after the perinatal stage. After P14, a third group of AROM-I neurons emerged in the lateral septal nucleus, the oval nucleus of the bed nucleus of the stria terminalis, and the central amygdaloid nucleus. The second group was thought to be the major aromatization center in developing rat brains, while the center might partly shift to the third group of neurons after the late infantile stage. The distribution and developmental patterns were basically similar in males and females, suggesting that the neonatally prominent aromatase is not induced by male-specific androgen surges occurring around birth. On immunoelectron microscopy, subneuronal aromatase was predominantly localized on the nuclear membrane and endoplasmic reticulum, which appeared to be appropriate for the efficient conversion of androgen into estrogen just prior to blinding to the nuclear receptors. © 1994 Wiley-Liss, Inc.     

Estrogen Receptor Immunoreactivity in Specific Brain Areas of the Prairie Vole (Microtus ochrogaster) is Altered by Sexual Receptivity and Genetic Sex

The prairie vole is a small rodent with an unusual reproductive strategy. A sexually naive female vole requires male contact to initiate the maturation of her reproductive functions. Contact with an unfamiliar adult male vole increases blood estrogen levels, reproductive tissue weights, and brain nuclear estrogen receptor binding levels of female voles. What is not known is: 1) What is the precise distribution of estrogen receptor containing neurons in the prairie vole brain? 2) Does male induced sexual receptivity alter the distribution or number of estrogen receptors in specific brain areas of the female vole? 3) Do male and female voles differ in the distribution or number of estrogen receptor containing neurons? We compared sexually receptive-male-exposed females, sexually naive females, and sexually naive males, for the presence of estrogen receptor immunoreactive (ER-IR) neurons in specific cell groups of the brain. The number of ER-IR neurons per cell group was counted and the relative amount of immunoreactivity per neuron was measured by densitometry. The neuroanatomical distribution of estrogen receptor containing neurons in the vole was similar to the distribution of estrogen receptors in most rodents. The mean number of ER-IR neurons did not differ between naive and male-exposed females. The induction of sexual receptivity however significantly decreased the concentration of estrogen receptor immunoreactivity per neuron in the medial preoptic nucleus, the medial preoptic area, the encapsulated bed nucleus of the stria terminalis, and the ventromedial nucleus of the hypothalamus. Compared with naive males, the mean number of ER-IR neurons was up to four fold greater in naive females in the medial preoptic nucleus, anteroventral periventricular preoptic nucleus, the encapsulated bed nucleus of the stria terminalis, the medial amygdala, and the ventromedial nucleus of the hypothalamus. Additionally the amount of estrogen receptor immunoreactivity per neuron was considerably greater in the medial preoptic nucleus, the medial preoptic area, the encapsulated bed nucleus of the stria terminalis, and the ventromedial nucleus of the hypothalamus of naive females. If the amount of estrogen receptor per cell is a determinant of a tissue's responsiveness to estrogen, reduced estrogen receptor immunoreactivity in males, and in females exposed to males suggests that they may be less responsive to estrogen than naive females. We propose that this reduced estrogen receptor immunoreactivity in males is a result of reduced estrogen receptor protein levels. Currently, we cannot definitively prove our working hypothesis that decreased estrogen receptor immunoreactivity in females exposed to males is due to reduced receptor levels, and not due to ligand altered epitope availability. Our working hypothesis is supported by the brain region-specific nature of our findings in the females. Experiments using additional antibodies directed against different epitopes of the estrogen receptor and examining ER mRNA will pursue this hypothesis. Brain regions in which estrogen receptor content differs depending upon genetic sex and experiential factors may be particularly important in the regulation of reproduction.     

Sex difference in dendritic development of the sexually dimorphic nucleus of the preoptic area in the rat

Sex differences in the growth and dendritic development of neurons in the sexually dimorphic nucleus of the preoptic area were examined with quantitative Golgi techniques during early postnatal life in rats. Neuronal size and dendritic extent were found to increase more in males than in females during the first 10 postnatal days, while the numbers of primary and terminal dendrites were similar in the two sexes. The onset of greater dendritic growth in males occurs just after the volume of the nucleus begins to exhibit sexual dimorphism, between 24 and 26 days after fertilization. Growth of dendrites in this region may be related to the presence of sex hormones during the critical period of sexual brain differentiation.     

Sex-specific patterns of galanin,cholecystokinin, and substance P expression in neurons of the principal bed nucleus of the stria terminalis are differentially reflected within three efferent preoptic pathways in the juvenile rat

Neurons in the principal bed nucleus of the stria terminalis (BSTp) integrate hormonal and sensory information associated with reproduction and transmit this information to hypothalamic nuclei that regulate neuroendocrine and behavioral functions. The neuropeptides galanin (GAL), cholecystokinin (CCK), and substance P (SP) are highly expressed in BSTp neurons and are differentially regulated by sex steroids. The current experiments investigated whether developmental or peripubertal hormone-mediated changes in GAL, CCK, and SP expression are reflected within efferent pathways to the preoptic structures that regulate gonadotropin secretion and sexual behavior. Anterograde labeling of projections from the BSTp of male and female juvenile rats combined with immunohistochemical labeling of GAL-, CCK-, and SP-containing fibers in the anteroventral periventricular preoptic nucleus (AVPV) and the central and medial divisions of the medial preoptic nucleus (MPNc, MPNm, respectively) revealed unique sex differences in each region. In the AVPV, Phaseolus vulgaris leucoagglutinin-labeled fibers were seen at a greater density in males than in females, and higher percentages of these fibers contained GAL in males than in females. In contrast, fibers projecting from the BSTp to the MPNc were more likely to contain SP in females than in males. Treatment of gonadectomized, peripubertal males and females with exogenous testosterone and estradiol did not alter the densities of GAL-, CCK-, or SP-containing fibers in any of the three brain areas examined. Collectively, these results suggest that patterns of neuropeptide expression in BSTp projections are established during development, resulting in a distinct, stable, and sex-specific chemoarchitectural profile for each projection pathway.     

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.