Biomedical subjects

N J MacLusky

Publications and source records attributed to N J MacLusky.

At least 37 records · Page 2Linked to original sources

PubMed1995

Sexual differentiation of estrogen receptor concentrations in the rat brain: effects of neonatal testosterone exposure.

This study tests the hypothesis that sex differences in estrogen receptor (ER) expression in the rat hypothalamus and preoptic area may at least partly result from androgen exposure during the immediate postnatal period. Male rats were castrated and female rats were injected with androgen, at either 15-30 min, 24 h or 10 days after birth. ER distribution in the brain was evaluated by in vitro autoradiography at 28 days of age. Males castrated immediately after birth exhibited higher ER levels in the preoptic area and the ventromedial and arcuate nuclei of the hypothalamus than either control males or males castrated on day 10. Females injected at birth with testosterone propionate exhibited reduced ER binding in the same brain regions. These data suggest that postnatal androgen secretion prior to postnatal day 10 permanently alters patterns of ER expression in the brain.

Analysis of Variance↗

PubMed1995

The effect of different hormone replacement therapy regimens on the mechanical properties of rat vertebrae.

The purpose of this study was to examine the effects of estrogen replacement, in concert with three different progestin regimens, on the mechanical properties of rat lumbar vertebrae. Ninety-two Sprague-Dawley rats (11 months old) were divided into six groups for treatment. The first group was an intact control, the second group (OVX) was ovariectomized only, and the third group (estrogen-only) was ovariectomized and received continuous estrogen through a 17 beta-estradiol implant. The remaining groups were ovariectomized and received estrogen and progestin (norethindrone, NET) therapy; 3 micrograms of NET was injected daily (estrogen plus continuous NET), or 6 micrograms of NET was injected for 14 consecutive days of a 28-day cycle (estrogen plus cyclic NET), or for 3 consecutive days of a 6-day cycle (estrogen plus interrupted NET). The animals were sacrificed after 6 months, and the vertebrae were dissected out. The vertebral processes of the fourth lumbar vertebrae were removed, and the density of the vertebral bodies was determined. They were then subjected to compression testing. We found that all three estrogen/progestin regimens maintain bone density and all mechanical properties at a level indistinguishable from the control. However, the cyclic and continuous NET treatment results were, with the exception of density, also indistinguishable from those of the ovariectomized group. The estrogen plus interrupted NET group on the other hand, has a significantly greater compressive modulus and density than the ovariectomized group. In conclusion, with respect to the ovariectomized group, the estrogen plus interrupted NET treatment resulted in a superior density and compressive modulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Lumbar vertebral density and mechanical properties in aged ovariectomized rats treated with estrogen and norethindrone or norgestimate.

OBJECTIVE: This study was designed to investigate the effects of estrogen alone or combined with two different progestins, norethindrone or norgestimate, on bone density and compressive mechanical properties in an aged rat model. STUDY DESIGN: Twenty 11-month-old female Sprague-Dawley rats were sham operated (intact control) and 80 wee ovariectomized. Three groups of 20 ovariectomized rats were implanted with Silastic silicon rubber (Dow Corning, Midland, Mich.) capsules containing 5% estradiol (wt/wt) in cholesterol. All rats in the intact control (group 1) and the ovariectomized (group 2) and the first of the ovariectomized plus estrogen (group 3) groups were injected subcutaneously daily for 6 months with corn oil (vehicle). Two other groups of rats with estrogen capsules received daily injections of norethindrone (3 micrograms/rat/day) or norgestimate (1.5 micrograms/rat/day) in corn oil for 3 days out of every 6 days (interrupted progestin). The effects of these various treatments on bone mineral content and bone mineral density in the vertebrae were measured by dual energy x-ray absorptiometry. The L4 vertebral bodies were also tested to failure in compression. RESULTS: The ovariectomized rats receiving corn oil alone had the lowest bone mineral density compared with intact controls. Estrogen treatment alone resulted in a lower bone mineral density than in the intact controls. In contrast, both interrupted progestin regimens resulted in vertebral bone mass index at the same level as the intact controls. Compression tests revealed that ovariectomized controls also had the lowest modulus of elasticity of all groups. However, unlike bone mineral density, estrogen alone resulted in mechanical properties similar to intact controls, whereas the vertebrae in both interrupted progestin groups had variable mechanical properties compared with the ovariectomized and intact control groups. CONCLUSIONS: We conclude that in this experimental model hormone replacement therapy with estrogen and an androgenic (norethindrone) or nonadrogenic (norgestimate) progestin result in similar bone mineral density and mechanical properties. In addition, both interrupted progestin regimens had a better effect than estrogen alone on vertebral bone density.

Absorptiometry, Photon↗

PubMed1995

Localization and measurement of occupied androgen receptors in thaw-mounted rat and human prostate tissue sections by in vitro autoradiography.

In this paper we present an in vitro exchange binding assay procedure for measurement of androgen receptors in slide-mounted tissue sections. This method allows quantitative autoradiographic determinations with an anatomical resolution approaching the cellular level. Tissue sections are incubated with the synthetic androgen [3H]R1881 in the presence of triamcinolone acetonide to suppress possible binding of the radioligand to the progestin receptor. Adjacent tissue sections are incubated with [3H]R1881 in the presence of excess unlabeled 5 alpha- dihydrotestosterone or R1881 to assess nonspecific binding. Following incubation, the tissue sections are washed to remove unbound radioligand and either scraped for immediate determination of androgen receptor binding or placed against emulsion-coated film for the production of an autoradiographic image. In validation experiments with rat prostate sections from castrated, gonad-intact, and androgen-supplemented animals, maximum levels of androgen binding were observed with incubation at 4 degrees C or 72 h. Markedly less binding was detected with shorter incubations or with incubations at even slightly elevated temperatures. Very little androgen receptor binding was detected in castrated animals whereas receptor levels in intact and androgen-supplemented animals were 79.3 fmol/mg and 143.6 fmol/mg protein, respectively, suggesting that the method is selective for occupied receptors. Saturation binding analysis revealed binding to a single class binding site with high affinity (kd = 1.475 +/- 0.12 nM). Autoradiographic images of androgen binding in the prostate reflected the findings with the scraped sections: essentially no specific binding was present in sections from castrated animals whereas much heavier labeling was present in sections from intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

In vitro labeling of gonadal steroid hormone receptors in brain tissue sections.

Autoradiographic methods have been developed for measurement of gonadal steroid receptors in situ in brain tissue sections. Based on principles established previously for estrogen receptors in the rat brain using a 125I-labeled ligand, procedures have been developed for in vitro labeling of estrogen, androgen, and progestin receptors with commercially available tritiated ligands. Addition of protamine sulfate to the incubation buffer precipitates the receptors in situ in the tissue sections, allowing them to be detected autoradiographically after incubation with labeled steroid and subsequent washing to remove unbound and nonspecifically bound ligand. Occupied and unoccupied estrogen receptors can be measured selectively using appropriately modified incubation conditions. In the case of androgen and progestin receptors, unoccupied receptors are readily detected by in vitro labeling of tissue sections, but occupied receptors do not appear to label efficiently. Preliminary data suggest that these methods should be equally applicable to a variety of laboratory animals, including the rat, mouse, guinea pig, and monkey.

Animals↗

PubMed1995

Immunocytochemical detection of androgen receptor in human temporal cortex characterization and application of polyclonal androgen receptor antibodies in frozen and paraffin-embedded tissues.

Immunocytochemical and biochemical studies have demonstrated the presence of androgen receptor protein in various regions of the rodent and non-human primate cortex. Localization of androgen receptor in the human brain has, however, not been studied as extensively, because of difficulties in obtaining suitable tissue samples. In the present study, we have localized androgen receptors in both frozen and paraffin-embedded temporal cortex from epileptic patients undergoing resection. Polyclonal antibodies were raised against fusion proteins containing fragments of the human androgen receptor protein. The antibodies were affinity-purified against the corresponding fusion protein. Immunoprecipitation and Western blotting using extracts from human cell lines demonstrated the specificity of the antibodies for the human androgen receptor and lack of cross-reactivity with other steroid hormone receptors. Immunocytochemistry was performed on frozen and paraffin sections of human temporal cortex and in paraffin-embedded benign hyperplastic prostates (BPH), as well as prostate and breast carcinomas, by the streptavidin-biotin-peroxidase method. Antigen-retrieval was performed in paraffin-embedded sections using microwave irradiation. Specific nuclear and cytoplasmic immunoreactivity for androgen receptor was detected in neurons, astrocytes, oligodendrocytes, and microglia cells of the temporal cortex. In contrast, only nuclear staining was observed in BPH, prostate and breast carcinomas. Immunoprecipitation of human temporal cortex lysate and subsequent Western blot analysis demonstrated the expression of a 98 kDa immunoreactive protein, slightly smaller than the reported molecular weight of the wild-type androgen receptor. These results provide further evidence for the expression of androgen receptor in the human temporal cortex. The use of these immunocytochemical techniques should enable the retrospective determination of possible changes in androgen receptor expression in a variety of archival paraffin-embedded tissues, including samples of the human central nervous system.

Adolescent↗

PubMed1995

Distribution of occupied and unoccupied estrogen receptors in the rat brain: effects of physiological gonadal steroid exposure.

In vitro autoradiographic methods have been developed for selective measurement of occupied and unoccupied estrogen receptors (ERs) in brain tissue sections. Addition of protamine sulfate traps unoccupied ERs in the tissue sections, allowing them to be detected after a short period of incubation with labeled estrogen. Occupied ERs are assessed, after washing in buffer without protamine to eliminate unoccupied receptor, by incubating the sections for 2 h at 37 C to exchange isotopically labeled steroid for the endogenous unlabeled ligand. Total ER binding capacity is estimated by summing the values for occupied and unoccupied ER. In all brain regions of normal females, ER occupation is low at estrus, reflecting the very low levels of circulating estradiol present at this stage of the estrous cycle, rising to approximately 50% of binding capacity at proestrus. By contrast, in intact males ER occupation varies considerably between brain regions, from a high of 55% of binding capacity in the bed nucleus of the stria terminalis to a low of 21% in the hypothalamic arcuate nucleus. Gonadectomy or treatment of intact males with the aromatase inhibitor 4-hydroxy androstenedione greatly reduces or eliminates ER occupation, depending on the brain region. In both sexes, changes in levels of endogenous gonadal steroids have little effect on total (occupied plus unoccupied) ER concentrations, with the exception of the hypothalamic ventromedial nucleus of the female, in which total ER concentration declines at estrus. These results are consistent with the hypothesis that local aromatization may be the primary determinant of regional ER occupation in the brain of the male rat, in contrast to the female, in which high levels of ER occupation are found only during the preovulatory estrogen surge. Although physiological changes in circulating estradiol and aromatizable androgen concentrations induce large changes in ER occupation, they have little effect on total ER content in most regions of the brain, suggesting that previous reports of changes in ER messenger RNA levels under different conditions of gonadal steroid exposure may not be directly reflected in steady state levels of the cognate receptor site.

Animals↗

PubMed1995

Hyaluronidase activity in human semen: correlation with fertilization in vitro.

OBJECTIVES: To characterize the relationship between hyaluronidase activity and the currently used methods of assessing sperm function and to determine whether the measurement of hyaluronidase activity can provide a reliable index of sperm fertilizing capacity in man. DESIGN: Nonrandomized prospective study. SETTING: Tertiary referral IVF and andrology clinics affiliated with the University of Toronto. SUBJECTS: Four hundred eight samples were collected, 248 from men undergoing investigation in andrology and fertility clinics and 160 from men participating in an IVF program. INTERVENTIONS: Semen samples were treated with NP-40 in buffer to extract hyaluronidase and applied to a circular well cut into a petri dish containing a mixture of hyaluronic acid and agar. Enzyme activity was assessed by measuring the area of substrate hydrolysis. RESULTS: Significant positive correlations were found between hyaluronidase activity and sperm concentration, motility, and the percentage of sperm with normal morphology in the studied samples. In the IVF samples, hyaluronidase activity was found to be related significantly to the fertilization rate. Moreover, we were able to establish values of hyaluronidase below which no fertilization occurred and above which fertilization of at least one oocyte was achieved. CONCLUSION: These results suggest that measurement of hyaluronidase activity may provide a useful method for assessing the integrity of the acrosomal enzyme system, providing a simple and reliable predictor of the fertilizing potential of human sperm.

Enzyme Stability↗

PubMed1995

The effect of three hormone replacement regimens on bone density in the aged ovariectomized rat.

OBJECTIVE: To investigate the effects of estrogen (E) alone or with cyclic, continuous, or interrupted P regimens on bone density in an aged rat model. DESIGN: Randomized controlled trial. ANIMALS: Twenty 12-month-old female Sprague-Dawley rats were sham operated (intact control) and 100 were ovariectomized (OVX). INTERVENTION: Four groups of 20 OVX rats were implanted with silastic capsules containing 5% E2 (wt/wt) in cholesterol. All rats in the intact control (group 1), OVX (group 2), and the first of the OVX plus E groups (group 3) were injected subcutaneously daily for 6 months with corn oil (vehicle). Three other groups of rats with E capsules received daily injections of norethindrone in corn oil, according to the following dosage schedules: 6 micrograms norethindrone/rat per day for 2 of every 4 weeks (cyclic; group 4); 3 micrograms norethindrone/rat per day every day (continuous; group 5); or 3 micrograms norethindrone/rat per day for 3 of every 6 days (interrupted; group 6). MAIN OUTCOME MEASURES: Bone mineral content (BMC) and bone mineral density (BMD) in the femur and vertebrae were measured by dual-energy roentgenogram absorptiometry. RESULTS: The OVX rats (group 2) receiving corn oil alone had the lowest BMD. Intact controls (group 1), E plus cyclic P (group 4), and E and interrupted P (group 6) were all similar and had significantly greater bone density in the vertebrae than the OVX controls. In contrast, vertebral BMD with E alone (group 3) and continuous E and P (group 5) was not significantly different from the OVX group. Femur BMD was significantly lower in the OVX group compared with the other five groups, which did not differ significantly from each other. CONCLUSION: In this experimental model, compared with OVX controls, combined hormone replacement therapy with E and cyclic or interrupted P resulted in the best vertebral BMD whereas continuous E and P resulted in the worst BMD. In the femurs, E alone and E plus P had equal effects on BMD.

Adrenal Glands↗

PubMed1994

Ontogenesis of prostaglandin E2 binding sites in the brainstem of the sheep.

Perinatal changes in plasma prostaglandin E2 (PGE2) act at the level of the fetal brainstem to modulate respiratory activity. In-vitro receptor autoradiography was used to determine whether PGE2 binding sites (putative receptors) are located in brainstem regions responsible for respiratory control. Frozen brainstem sections were obtained from fetal sheep at 140 d of gestation, lambs at 5 h and 10 d after birth, and adults (n = 3 at each age). In the perinatal brainstem, high density binding was localized near the following nuclei: hypoglossal, tractus solitarius, parabrachial and spinal trigeminal-oral. Moderate levels of binding were localized near the nuclei of the spinal trigeminal tract, ambiguus, inferior olivary, cuneate, gracilis, facial, medial vestibular, superior vestibular, and abducens. Binding density did not change with age within the perinatal period. However, binding in three high density regions (hypoglossal, spinal trigeminal and parabrachial nuclei) decreased significantly in adulthood, whereas the binding in the nucleus of the solitary tract remained high. We hypothesize that the PGE2 binding sites that we identified near respiratory regions of the brainstem may mediate the central respiratory effects of PGE2.

Animals↗

PubMed1994

Sex differences in the development of estrogen receptors in the rat brain.

The mechanisms involved in sexual differentiation of the brain remain incompletely defined. In mammals, testosterone secretion by the male during early development permanently alters the capacity of the brain to respond to circulating estrogen. In rats, this change in estrogen responsiveness is associated with a reduction in estrogen receptor (ER) levels in the periventricular region of the preoptic area (PVP), the medial preoptic nucleus (MPO), and the hypothalamic ventromedial nucleus (VMN) of the male. To determine whether these differences represent a response to early testosterone exposure or a secondary consequence of gonadal secretions at puberty, ER levels were measured by quantitative in vitro autoradiography in the brains of rats killed at intervals between 1-10 and 28-49 days of age. As early as 24 hr after birth, ER sex differences in the MPO and PVP are already quantitatively similar to those observed in adulthood. A sex difference in the VMN emerges later, between 5 and 10 days of age. Differences between brain regions are also observed in the rate of ER development after the first week of life, ER concentrations in the PVP and MPO being close to adult levels within 1 day of birth, in contrast to the VMN where they increase markedly between Day 10 and adulthood in both sexes. These observations suggest that changes in ER concentrations may be one of the earliest hallmarks of brain sexual differentiation. Sex differences in ER in different brain regions may, however, be expressed asynchronously, providing a possible mechanism for variation in the duration of "critical periods" for testosterone-mediated organization of specific CNS functions.

Animals↗

PubMed1994

Progesterone modulation of estrogen receptors in microdissected regions of the rat hypothalamus.

One mechanism whereby progesterone opposes the regulatory actions of estrogen in the brain may include the down-regulation of estrogen receptors. A previous study has shown a small decrease in estrogen binding in the combined preoptic area-hypothalamic area in response to progesterone treatment. To determine if this effect is region specific, gonadectomized/adrenalectomized (GDX/ADX) estrogen-treated female rats were administered a single injection of progesterone (5.0 mg, sc) or a silastic capsule containing crystalline progesterone. Control animals were treated identically but without progesterone exposure. Animals were killed 24 or 72 h after initiating progesterone treatment and estrogen binding was measured in cytosol and cell nuclear extracts of the anterior pituitary, mediobasal hypothalamus (MBH), and preoptic area. A significant effect of progesterone injection on nuclear estrogen binding was observed in the MBH at 24 h. This effect had subsided by 72 h. No effect was observed when progesterone was administered in a continuous fashion. To further examine the regional specificity of the progesterone effect and to determine if males were similarly affected, nuclear-bound estrogen receptors were measured in microdissected brain regions from male and female estrogen-treated GDX/ADX rats treated with 5.0 mg progesterone or vehicle 24 h before sacrifice. A significant decrease in estrogen binding was found in the ventromedial nucleus of the female but not the male. A significant effect of progesterone treatment was found in the periventricular preoptic area of the male.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

PubMed1994

Pubertal development of estrogen receptors in the rat brain.

The regional distribution of estrogen receptors (ER) was studied in the brain of the female rat over the peripubertal period. Increases were observed in nuclear ER occupation as well as cytosolic progestin receptor induction in the period leading up to the time of vaginal opening, consistent with an increased availability of estrogen to the brain. ER binding capacity, however, was remarkably similar in pre- and postpubertal rats. Using a microdissection-based nuclear ER assay, small increases in the total ER content of the hypothalamic ventromedial and arcuate nuclei were observed in the female at around the time of the onset of reproductive cyclicity. In vivo autoradiographic studies confirmed the existence of a small increase in estrogen binding in these two brain regions at around the time of vaginal opening, as well as transient increases in estrogen retention within the preoptic area and bed nucleus of the stria terminalis. These changes in estrogen binding in the brain may play a role in pubertal alterations in the feedback sensitivity of the brain to circulating estrogen.

Aging↗

PubMed1994

Androgen treatment decreases estrogen receptor binding in the ventromedial nucleus of the rat brain: a quantitative in vitro autoradiographic analysis.

Androgens oppose the actions of estrogen on a number of neuroendocrine functions in the rat including prolactin and gonadotropin secretion and the activation of the female pattern of sex behavior. Although in nonneural tissues antiestrogenic actions of androgens have been related to actions at the level of the estrogen receptor, previous attempts to demonstrate effects of nonaromatizable androgens on estrogen receptor levels in the brain have been unsuccessful, possibly because of the poor anatomical resolution of the methods used. We have used a new in vitro autoradiographic assay combined with an 125I-labeled estrogen receptor ligand to test the hypothesis that the nonaromatizable androgen, 5 alpha-dihydrotestosterone (5 alpha-DHT), may act to reduce estrogen binding in specific regions of the brain involved in reproductive neuroendocrine and behavioral responses. This in vitro autoradiographic method allows selective measurement of occupied estrogen receptors in tissue sections. Gonadectomized/adrenalectomized rats were divided into two groups per sex. All animals received daily injections of estradiol benzoate (EB: 40 micrograms/kg body wt) for 4 days. Animals in the 5 alpha-DHT treatment group received 5 alpha-DHT (10 mg/kg body wt) every 12 h for 4 days, while animals in the control group received vehicle injections. Animals were killed 4 h after the final EB/5 alpha-DHT injection and their brains processed for in vitro autoradiography. As previously reported, higher levels of estrogen binding were observed in the ventrolateral aspect of the ventromedial nucleus (vIVMN) and the periventricular and medial preoptic area of the female compared to the male.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

PubMed1994

Aromatase in the cerebral cortex, hippocampus, and mid-brain: ontogeny and developmental implications.

Aromatase activity was measured in explant cultures from the newborn mouse and rat brain and in homogenates of regions of the rat brain sampled between birth and 51 days of age. Conversion of 19-[3H]hydroxy-androstenedione to estradiol and estrone was detected in explant cultures from the mouse preoptic/septal region, anterior cingulate cortex, and midbrain, as well as from the rat preoptic area, septum, hippocampus, anterior cingulate cortex, and midbrain central grey. No detectable estrogen biosynthesis was observed in explants from the cerebellum and spinal cord of either species. Measurements of aromatase in tissue homogenates using 1 beta[3H]androstenedione as substrate revealed detectable enzyme activity in the hypothalamus + preoptic area, amygdala, hippocampus, anterior cingulate cortex, and midbrain, from birth onward. Aromatase activity per milligram of tissue protein was highest in the hypothalamus-preoptic area and amygdala, followed by the hippocampus, midbrain, and cingulate cortex. In all brain regions, aromatase activity was markedly higher at Postnatal Days 1 and 7 than later in life. In both the cingulate cortex and the hippocampus, aromatase was barely detectable above the assay blank in adult (51 day) animals. These results demonstrate that regions of the developing rodent neo- and archicortex have the capacity to convert androgen to estrogen, consistent with a role for local estrogen biosynthesis in the sexual differentiation of higher brain functions.

Aging↗

PubMed1994

Partial demasculinization and feminization of sex behavior in male rats by in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin is not associated with alterations in estrogen receptor binding or volumes of sexually differentiated brain nuclei.

In utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure partially demasculinizes and feminizes sexual behavior in adult male rats, presumably by causing incomplete sexual differentiation of the central nervous system (CNS). Our objective was to determine if TCDD exposure affects other aspects of sexual differentiation of the CNS. Because sex differences in the estrogen receptor system are thought to play a role in sexually dimorphic estrogen-mediated responses, and because estrogen is an important activator of both male and female sex behavior, the possible effect of TCDD exposure on estrogen binding in specific brain nuclei was examined. In addition, we investigated effects of in utero and lactational TCDD exposure on sex differences in the volumes of brain nuclei which are dependent on steroid hormone stimulation during the period of CNS sexual differentiation. Pregnant Holtzman rats were given TCDD (0.7 microgram/kg, po) or vehicle (control) on gestation Day 15. Offspring were exposed to TCDD in utero and via lactation and then assessed in adulthood. Demasculinized sexual behavior was evidenced in the TCDD-exposed males by increased intromission latencies and a greater number of intromissions prior to ejaculation. These males were then castrated, primed with ovarian steroids, and tested for feminine sexual behavior. In utero and lactational TCDD exposure increased both the frequency and intensity of lordotic behavior, indicating that the males were partially feminized. To determine if TCDD exposure had a generalized effect on estrogen receptor concentrations the arcuate nucleus, cortical and medical amygdala and the bed nucleus of the stria terminalis, previously found to have equivalent numbers of estrogen receptors in males and females, were evaluated in littermates of the rats whose sexual behavior had been assessed. TCDD had no effect in either sex. To determine if TCDD exposure had an effect specific to sexual differentiation of the brain, estrogen receptor concentrations in the medial preoptic nucleus (MPO), ventrolateral aspect of the ventro-medial nucleus, and periventricular preoptic area were assessed. As expected, females had higher estrogen receptor concentrations in these nuclei than did males, but TCDD exposure did not affect estrogen receptor concentrations in any of these sexually dimorphic brain nuclei. The volumes of sexually dimorphic brain nuclei were examined in additional littermates. In control rats, the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) is larger in males than in females whereas the MPO is larger in females than in males. TCDD exposure had no effect on the volume of either the SDN-POA or MPO in either males or females.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Dexamethasone partially protects the myometrium against beta-adrenergic agonist-induced desensitization in vivo in the rat.

OBJECTIVE: Our purpose was to determine the ability of dexamethasone to prevent the onset of myometrial desensitization to beta-adrenergic agonists in vivo. STUDY DESIGN: On day 5 post partum chronically catheterized rats were randomized to receive either dexamethasone or corn oil (vehicle), followed 12 hours later by a continuous infusion of either isoproterenol or saline solution (vehicle). Uterine contractions were monitored throughout. We measured myometrial glucocorticoid receptor levels in chronically catheterized and sham-operated rats and beta 2-adrenergic receptor densities in the experimental rats before and during the infusions. RESULTS: Surgery did not lead to any decrease in glucocorticoid receptor number. Dexamethasone significantly increased the duration of myometrial responsiveness to isoproterenol compared with vehicle-pretreated rats, although agonist-induced down-regulation of beta-adrenergic receptor number was not prevented. CONCLUSION: Dexamethasone partially protects the rat myometrium from desensitization induced by the continuous infusion of beta-adrenergic agonists through mechanisms independent of the beta 2-receptor.

Adrenergic beta-Agonists↗

PubMed1993

Neural aromatase activity in a marsupial, the gray short-tailed opossum (Monodelphis domestica): ontogeny during postnatal development and androgen regulation in adulthood.

Neural aromatase activity (AA) was measured in gray short-tailed opossums (Monodelphis domestica) on the day of birth and at selected ages through adulthood. In adulthood, regulation by testicular androgens was examined. In mixed-sex samples of whole brain, AA was present at birth and increased until postnatal day (PD) 16. In hypothalamus-preoptic area (HPOA), significantly higher levels of AA were seen in animals on PD 16 than on PD 30 and PD 30 animals had higher levels of AA than all older ages including adults. Significant sex differences in HPOA AA with male levels higher, were seen only on PD 16 and in adulthood. While lower overall than in HPOA, AA was present also in cerebral cortex (CX). In CX, AA was higher on PDs 16 and 30 than at older ages. Significant sex differences in CX AA were observed only in adulthood. One week following castration in adulthood, AA dropped significantly in CX but not in HPOA. These findings are compared with those obtained from other marsupial and eutherian mammals with reference to the possible significance of AA in sexual differentiation of the gray opossum brain.

Androgens↗