Biomedical subjects

R A Gorski

Publications and source records attributed to R A Gorski.

At least 19 recordsLinked to original sources

PubMed1994

Differential cDNA cloning by enzymatic degrading subtraction (EDS).

We describe a new method, called enzymatic degrading subtraction (EDS), for the construction of subtractive libraries from PCR amplified cDNA. The novel features of this method are that i) the tester DNA is blocked by thionucleotide incorporation; ii) the rate of hybridization is accelerated by phenol-emulsion reassociation; and iii) the driver cDNA and hybrid molecules are enzymatically removed by digestion with exonucleases III and VII rather than by physical partitioning. We demonstrate the utility of EDS by constructing a subtractive library enriched for cDNAs expressed in adult but not in embryonic rat brains.

Animals↗

PubMed1994

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.

Animals↗

PubMed1992

Sexual orientation and the size of the anterior commissure in the human brain.

The anterior commissure, a fiber tract that is larger in its midsagittal area in women than in men, was examined in 90 postmortem brains from homosexual men, heterosexual men, and heterosexual women. The midsagittal plane of the anterior commissure in homosexual men was 18% larger than in heterosexual women and 34% larger than in heterosexual men. This anatomical difference, which correlates with gender and sexual orientation, may, in part, underlie differences in cognitive function and cerebral lateralization among homosexual men, heterosexual men, and heterosexual women. Moreover, this finding of a difference in a structure not known to be related to reproductive functions supports the hypothesis that factors operating early in development differentiate sexually dimorphic structures and functions of the brain, including the anterior commissure and sexual orientation, in a global fashion.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Sex differences in subregions of the medial nucleus of the amygdala and the bed nucleus of the stria terminalis of the rat.

Sex differences are described in subregions of two nuclei of the rat brain: the medical nucleus of the amygdala (MA) and the bed nucleus of the stria terminalis (BNST). The volume of the posterodorsal region of the medial nucleus of the amygdala (MApd) is approximately 85% greater and the volume of the encapsulated region of the bed nucleus of the stria terminalis (BNSTenc) is approximately 97% greater in males than in females. The MApd and BNSTenc are distinct subregions of the MA and BNST. They exhibit intense uptake of gonadal hormones and are anatomically connected to each other and to other sexually dimorphic nuclei. The MA and BNST in general are involved in regulation of several sexually dimorphic functions, including aggression, sexual behavior, gonadotropin secretion and integration of olfactory information. Precise localization of sex differences in subregions of the MA and BNST, such as the MApd and BNSTenc, may facilitate understanding of the neural basis of such functions.

Amygdala↗

PubMed1992

Effects of thymectomy on reproductive function and behavior.

The effects of thymectomy in perinatal Long-Evans rat pups on their reproductive function in early adulthood were examined. Thymectomized females had decreased lordotic responsivity to estrogen, while thymectomized males exhibited differences in mount latency or postejaculatory interval; these results suggest a possible influence of the thymus on the normal development of the neural substrates of sexual behavior. Gonadal histology appeared unperturbed in rats of either sex. No statistical abnormalities in luteinizing hormone or testosterone levels were seen in male animals. Likewise, no disturbances were observed in the ability of females to exhibit normal positive feedback after estrogen and progesterone administration; negative feedback after unilateral ovariectomy (as judged by ovarian compensatory hypertrophy) was also normal. The timing of puberty was not statistically delayed in females, even though slowed growth rates were observed. A heightened surgical stress response, as judged by progesterone levels in experimental females, suggests that perinatal thymectomy may possibly alter the sensitivity of adults to stress.

Animals↗

PubMed1991

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.

Aging↗

PubMed1991

Prenatal ethanol and the prepubertal sexually dimorphic nucleus of the preoptic area.

The volume of the sexually dimorphic nucleus of the preoptic area of the hypothalamus (SDN-POA) was determined in 14-31-day-old male and female rats whose mothers received a liquid diet containing 5% w/v ethanol from day 8 of gestation to parturition. Pair-fed dams received as a nutritional control an equal volume of an isocaloric liquid diet with maltose-dextrin in place of ethanol. Normal controls had laboratory rat chow and water available ad lib. The SDN-POA volume of ethanol-exposed males was significantly reduced compared to the pair-fed and normal males, and became indistinguishable from the SDN-POA volumes of the pair-fed and normal females. Ethanol-treated females also had a markedly reduced SDN-POA volume compared to the pair-fed and normal females. Our findings indicate that the SDN-POA of prepubertal rats of both sexes is sensitive to the effects of in utero ethanol exposure. While plasma testosterone, progesterone and estradiol titers, which we measured in fetuses on gestation day 22, were differentially affected by maternal ethanol consumption, the alterations by themselves cannot adequately explain the effects of prenatal ethanol exposure on the developing SDN-POA.

Animals↗

PubMed1991

Sex differences in the corpus callosum of the living human being.

The sexual dimorphism of the corpus callosum has remained controversial since the original report by de Lacoste-Utamsing and Holloway in 1982, for several reasons: (1) measurements have been performed in a variety of ways in different laboratories, in part because published reports frequently do not describe the methodology in detail; (2) despite known age-related changes during both childhood and adulthood, no investigators have explicitly age-matched subjects; and (3) the size and shape of corpora callosa vary considerably among individuals, requiring large sample sizes to demonstrate significant sex differences. Therefore, we have examined magnetic resonance images for 24 age-matched children and 122 age-matched adults for possible sex differences in the corpus callosum. While we observed a dramatic sex difference in the shape of the corpus callosum, there was no conclusive evidence of sexual dimorphism in the area of the corpus callosum or its subdivisions. Utilizing several criteria, there were significant sex differences in shape: subjective evaluation indicated that the posterior region of the corpus callosum, the splenium, was more bulbous shaped in females as a group and in women, and more tubular-shaped in males as a group and in men; mathematical evaluation confirmed this observation in that the maximum width of the splenium was significantly greater in women than in men, and that the percentage by which the average width of the splenium was greater than that of the adjacent corpus callosum was significantly greater in females than in males. However, sex differences in bulbosity did not reach significance in children (aged 2-16 yr). In contrast, among the area measurements of the corpus callosum and 22 subdivisions, only 1 exhibited a significant sex difference, which would be expected by chance. The area of the corpora callosa increased significantly with age in children and decreased significantly with age in adults. In adults, the midsagittal surface area of the cerebral cortex decreased significantly with age in women but not in men. These anatomical sex differences could, in part, underlie gender-related differences in behavior and neuropsychological function.

Adolescent↗

PubMed1990

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.

Adolescent↗

PubMed1990

Prenatal inhibition of hypothalamic sex steroid uptake by cocaine: effects on neurobehavioral sexual differentiation in male rats.

Several adrenergically active drugs have been shown to prevent the masculinizing and/or defeminizing effects of testosterone on brain sexual differentiation. We examined the ability of the neuronal norepinephrine uptake blocker, cocaine, to produce similar effects. The ability of cocaine to inhibit sex steroid incorporation into the hypothalamus during a critical period for sexual differentiation of the brain was examined in females treated at birth with testosterone. Sixty minutes after administration, cocaine was observed to inhibit both testosterone and estradiol incorporation into the hypothalamus by approximately 50%. Long-term consequences of prenatal cocaine exposure were studied by injecting Sprague-Dawley dams twice daily with 3, 10 or 30 mg/kg of cocaine hydrochloride on days 15 through 20 of gestation and examining the offspring. In adulthood, cocaine-exposed males, but not females were found to exhibit significantly less marking behavior than controls. Cocaine-exposed males in the 10 mg/kg group tested for sex behavior exhibited demasculinization in some aspects of the behaviors tested. Measurement of plasma hormone levels in this group revealed elevated levels of plasma LH, but normal levels of FSH and testosterone. No differences were observed in cocaine-exposed males with respect to sex organ or adrenal weights, but thymus was approximately 25% smaller compared to control males at 80 days of age. In a separate experiment, dams were treated with 3 mg/kg of cocaine twice daily from days 15 through 21 of gestation and half of the male pups received additional injections twice a day for the first 5 days postnatally.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Termination of the hormone-sensitive period for differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats.

The volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in the rat brain is several-fold larger in males than in females. The volume of the SDN-POA can be influenced significantly by the hormone milieu during early postnatal life. The purpose of the present study was to identify when termination of the sensitive period occurs during which exogenous androgen administration influences SDN-POA volume in males gonadectomized on the first day of postnatal life (fales) or intact females. Analysis of the SDN-POA in fales showed that testosterone propionate (TP, 500 micrograms) treatment on days 2, 3, 4, or 5, significantly increased its volume over values from oil-treated fales. In contrast, TP treatment in fales on days 6, 7, or 8, failed to increase SDN-POA volume. A similar pattern was observed in females treated with TP. Females treated with TP (500 micrograms) on days 2, 3, 4, or 5, showed a significant increase in SDN-POA volume compared to the values from oil-injected animals, while the same TP treatment in females on days 6, 7, or 8, resulted in no such enhancement. The absolute and relative change in SDN-POA volume following postnatal androgen treatment is greater in males than in females. We conclude that (1) SDN-POA development is sensitive to hormone action through postnatal day 5 and then abruptly becomes insensitive to this dosage of TP, and (2) although the temporal pattern of the response is similar in males and females, androgen exposure postnatally results in a consistently greater increase in the male SDN-POA volume than in the female's. This greater response may be due to exposure prenatally to endogenous androgen in males.

Aging↗

PubMed1990

Onset of the hormone-sensitive perinatal period for sexual differentiation of the sexually dimorphic nucleus of the preoptic area in female rats.

The volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of the rat brain is severalfold larger in males than in females. The volume of the SDN-POA can be influenced significantly by the hormonal milieu during the perinatal "critical period" of sexual differentiation of the brain. The purpose of the present study was to determine the onset of this period of sexual differentiation of the SDN-POA. Pregnant rats received no treatment or were injected subcutaneously with oil on day 17, 18, or 20, or testosterone (T;5 mg) on days 16-22 of gestation. On postnatal day 15, unilateral SDN-POA volumes from female offspring prenatally exposed to testosterone on day 16 or 17 were not different from values of control (untreated or oil-injected) offspring. Female offspring from mothers treated with testosterone on day 18, 19, or 20 of gestation showed a significant and similar increase in SDN-POA volume over values from control animals. SDN-POA volumes from female offspring exposed to testosterone on day 21 or 22, although larger than those of controls, were not different statistically. We conclude that with the specific paradigm used in this study SDN-POA development is insensitive prior to day 18 of gestation, the day on which the onset of the hormone-sensitive period occurs.

Animals↗

PubMed1989

Effects of site-specific CNS microinjection of cholecystokinin on lordosis behavior in the male rat.

We have previously demonstrated that intracerebroventricular injections of sulphated cholecystokinin octapeptide (sCCK-8) had a dramatic facilitatory effect on lordosis behavior in the gonadectomized, estrogen-primed male rat. In the female, sCCK-8 facilitates or inhibits lordosis when microinjected into the medial preoptic nucleus (MPN) or ventromedial nucleus of the hypothalamus (VMH), respectively. In order to identify sCCK-8 responsive sites that modulate lordosis behavior in gonadectomized males, sCCK-8 was microinjected into the MPN or VMH. Sulphated CCK-8 significantly increased lordosis behavior when microinjected into the MPN of estrogen-primed males, but had no significant effects when microinjected into the VMH. These results imply that CCK-sensitive neural substrates within the MPN may act to disinhibit lordosis in the gonadectomized, estrogen-primed male rat. The lack of an effect of VMH injection of sCCK-8 on lordosis in males is discussed in terms of possible sex differences in sCCK-8-sensitive lordosis-modulating circuits.

Animals↗

PubMed1989

Two sexually dimorphic cell groups in the human brain.

A quantitative analysis of the volume of 4 cell groups in the preoptic-anterior hypothalamic area (PO-AHA) and of the supraoptic nucleus (SON) of the human brain was performed in 22 age-matched male and female individuals. We suggest the term Interstitial Nuclei of the Anterior Hypothalamus (INAH 1-4) to identify these 4 previously undescribed cell groups in the PO-AHA. While 2 INAH and the SON were not sexually dimorphic, gender-related differences were found in the other 2 cell groups. One nucleus (INAH-3) was 2.8 times larger in the male brain than in the female brain irrespective of age. The other cell group (INAH-2) was twice as large in the male brain, but also appeared to be related in women to circulating steroid hormone levels. Since the PO-AHA influences gonadotropin secretion, maternal behavior, and sexual behavior in several mammalian species, these results suggest that functional sex differences in the hypothalamus may be related to sex differences in neural structure.

Adolescent↗

PubMed1988

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.

Animals↗

PubMed1988

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.

Age Factors↗

PubMed1988

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)

Aging↗

PubMed1988

Postnatal influence of diethylstilbestrol on the differentiation of the sexually dimorphic nucleus in the rat is as effective as perinatal treatment.

The volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of the male rat brain is larger than that of the female. In the female rat, treatment with diethylstilbestrol (DES), either perinatally (from day 16 of gestation to postnatal day 10), or postnatally (birth to day 10) was equally effective in increasing the volume of SDN-POA compared to controls. Prenatal treatment (day 16 of gestation to birth) with DES also increased the volume of the SDN-POA but this increase was significantly smaller than that achieved with the other treatments. These results confirm the effectiveness of DES in increasing the volume of the SDN-POA in the female rat brain, and prove that the differentiating SDN-POA is very receptive to hormone influences in the early postnatal period.

Aging↗