Search PubMed⌕ Search

Biomedical subjects

S K Mani

Publications and source records attributed to S K Mani.

17 recordsLinked to original sources
PubMed2003

Induction of Fos in the accessory olfactory system by male odors persists in female mice with a null mutation of the aromatase (cyp19) gene.

The ability of odors from soiled male bedding to induce neuronal Fos-immunoreactivity (IR) in sensory neurons located in both the apical and basal zones of the vomeronasal organ (VNO) and in two segments of the VNO-projection pathway, the anterior nucleus of the medial amygdala and the bed nucleus of the stria terminalis (BNST), was significantly reduced in adult, ovariectomized, estrogen-treated female mice with a homozygous null mutation of the cyp19 gene (ArKO) which encodes the estrogen biosynthetic P450 enzyme, aromatase. However, a significant odor-induced activation of Fos-IR was seen in other segments of the VNO-projection pathway of ArKO females, including the accessory olfactory bulb (AOB) granule cell layer, the posterior-dorsal medial amygdala (MePD), and the medial preoptic area (MPA). These results suggest that the VNO/accessory olfactory pathway to the hypothalamus was functional in ArKO females even though they had presumably been exposed to less estrogenic stimulation than wild-type (WT) control females throughout development and until the time that estrogen treatment was begun in adulthood. Thus, the hypothesis of Toran-Allerand [Prog. Brain Res. 61 (1984) 63] that female-typical features of neuroendocrine and behavioral function require perinatal exposure to estrogen was not supported, at least for the VNO/accessory olfactory system.

Animals↗
PubMed2001

Progesterone receptor and dopamine receptors are required in Delta 9-tetrahydrocannabinol modulation of sexual receptivity in female rats.

Ovarian steroids, estrogen and progesterone, influence the sensitivity of certain neural processes to cannabinoid treatment by modulation of brain dopaminergic activity. We examined the effects of the active ingredient of cannabis, Delta(9)-tetrahydrocannabinol (THC), on sexual behavior in female rats and its influence on steroid hormone receptors and neurotransmitters in the facilitation of sexual receptivity. Our results revealed that the facilitatory effect of THC was inhibited by antagonists to both progesterone and dopamine D(1) receptors. To test further the idea that progesterone receptors (PR) and/or dopamine receptors (D(1)R) in the hypothalamus are required for THC-facilitated sexual behavior in rodents, antisense and sense oligonucleotides to PR and D(1)R were administered intracerebroventricularly (ICV) into the third cerebral ventricle of ovariectomized, estradiol benzoate-primed rats. Progesterone- and THC-facilitated sexual behavior was inhibited in animals treated with antisense oligonucleotides to PR or to D(1)R. Antagonists to cannabinoid receptor-1 subtype (CB(1)), but not to cannabinoid receptor-2 subtype (CB(2)) inhibited progesterone- and dopamine-facilitated sexual receptivity in female rats. Our studies indicate that THC acts on the CB(1) cannabinoid receptor to initiate a signal transduction response that requires both membrane dopamine and intracellular progesterone receptors for effective induction of sexual behavior.

Animals↗
PubMed2000

Requirement for DARPP-32 in progesterone-facilitated sexual receptivity in female rats and mice.

DARPP-32, a dopamine- and adenosine 3',5'-monophosphate (cAMP)-regulated phosphoprotein (32 kilodaltons in size), is an obligate intermediate in progesterone (P)-facilitated sexual receptivity in female rats and mice. The facilitative effect of P on sexual receptivity in female rats was blocked by antisense oligonucleotides to DARPP-32. Homozygous mice carrying a null mutation for the DARPP-32 gene exhibited minimal levels of P-facilitated sexual receptivity when compared to their wild-type littermates. P significantly increased hypothalamic cAMP levels and cAMP-dependent protein kinase activity. These increases were not inhibited by a D1 subclass dopamine receptor antagonist. P also enhanced phosphorylation of DARPP-32 on threonine 34 in the hypothalamus of mice. DARPP-32 activation is thus an obligatory step in progestin receptor regulation of sexual receptivity in rats and mice.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2000

Solar photo-oxidative disinfection of drinking water: preliminary field observations.

The feasibility of using solar photo-oxidation to inactivate faecal bacterial contaminants in drinking water has been evaluated under field conditions in India and South Africa. Freshly drawn samples from all six test water sources were low in dissolved oxygen, at 13-40% of the air saturation value. However, vigorous mixing followed by exposure to full-strength sunlight in transparent plastic containers (1-25 l capacity) caused a rapid decrease in the counts of faecal indicator bacteria, giving complete inactivation within 3-6 h, with no evidence of reactivation. These results demonstrate that solar photo-oxidation may provide a practical, low-cost approach to the improvement of drinking water quality in developing countries with consistently sunny climates.

Colony Count, Microbial↗
PubMed1998

Reduction of mucin-1 expression during the receptive phase in the rat uterus.

Mucin-1 (Muc1), an integral membrane mucin, is expressed on the apical surface of uterine epithelial cells (UE) of various species. Loss of Muc1 is believed to be necessary for embryo attachment. Muc1 expression is markedly reduced in luminal epithelia during the receptive phase in mice, baboons, and pigs. In the present study, we examined Muc1 expression during the rat estrous cycle and at Day 5 of pregnancy, the time of embryo attachment. In contrast to findings in the mouse, indirect immunofluorescence revealed that uterine Muc1 protein expression was unaltered during the estrous cycle. However, similar to what is observed in the mouse and other species, Muc1 protein decreased at Day 5 of pregnancy in luminal UE. The decrease in Muc1 expression was specific to luminal UE and did not occur in glandular UE. A partial cDNA corresponding to the cytoplasmic tail region of rat Muc1 was generated by a reverse transcription-polymerase chain reaction (RT-PCR) strategy. This cDNA sequence is 89% and 91% identical to the corresponding region of mouse Muc1 at the nucleotide and amino acid levels, respectively. The predicted sequence of rat Muc1 protein has 70-90% identity to the Muc1 protein sequence obtained in other species. Semiquantitative RT-PCR experiments indicated that the mRNA encoding rat Muc1 decreased 57% at Day 5 as compared with the levels found at estrus. This value included mRNA from both luminal and glandular UE and so may underestimate the relative decrease in mRNA in the luminal compartment. In conclusion, we have determined that the levels of rat Muc1 protein and mRNA decrease in the luminal UE at the time of implantation, a pattern similar to that seen in the mouse, baboon, and pig. This supports the general theory that reduction of Muc1 expression is necessary for embryo implantation.

Amino Acid Sequence↗
PubMed1997

Progesterone receptor function from a behavioral perspective.

Hormonal induction of sexual receptivity in ovariectomized female mice can be effectively reinstated by sequential administration of estradiol and progesterone. In this regard, mice appear to be similar to other rodents. While it is generally accepted that hypothalamic progesterone receptors function as estradiol-induced transcription factors in the induction of sexual receptivity in rats, hamsters, and guinea pigs, relatively little is known about their role in the mouse, a species which exhibits genotypic and strain differences in the responsiveness to steroid hormones. Using a transgenic mouse carrying a null mutation for the progesterone receptor by gene targeting, we examined the role of the progesterone receptor as a coordinator of key regulatory events in the induction of sexual receptivity. A concordance between hypothalamic progesterone receptor levels and behavioral responsiveness was established by comparing the homozygous mutant, heterozygous mutant, and wild-type littermates. The behavioral and biochemical findings reveal the importance of estradiol-induced progesterone receptors for the expression of sexual behavior in female mice. The behavioral response of the two parental mouse strains from which the recombinant genotype was generated was also examined. As an extension of our earlier studies on the ligand-independent activation of progesterone receptors by neurotransmitters, the behavioral effect of dopamine in the facilitation of sexual receptivity in mice was also examined. The studies provide further evidence that steroid hormone receptors function as general transcription factors to achieve the integration of neural information in the central nervous system, and they assign a more important role for progesterone receptors than hitherto envisioned.

Animals↗
PubMed1996

Dopamine requires the unoccupied progesterone receptor to induce sexual behavior in mice.

Using the recently generated mutant mice strain (PRKO) carrying a null mutation for the progesterone receptor (PR) gene by gene targeting, we examined the critical role of PR as a coordinator of key regulatory events involved in the steroid hormone and dopamine-facilitated sexual behavior in female mice. In vitro one-point binding analyses of estradiol benzoate (EB)-induced cellular PRs and immunohistochemistry of PR in the mediobasal hypothalamus demonstrated a reduction in binding in the homozygous females, equivalent to background levels seen in EB-unresponsive tissue. The biochemical findings correlated well with the behavioral observations, with the wild type females exhibiting high levels of lordosis, while the homozygous females showed minimal lordosis in response to mating by male mice. As a critical validation of our earlier studies on ligand-independent activation of PRs by dopamine, we examined the facilitation of sexual behavior by a dopamine agonist in the null mutants. Wild type females having the full complement of PRs exhibited high levels of lordosis, while the homozygous females showed minimal lordosis in response to dopamine. To determine whether this reduced response was due to a general lack of ability to express lordosis, mice were treated with another neurotransmitter, serotonin. No significant difference in the serotonin-facilitated lordosis response was observed between the wild type and the homozygous females. We conclude that multiple signal transduction pathways coexist in the neuroendocrine system for reproductive behavior, with PR acting as a transcriptional mediator for dopamine, as well as progesterone, to achieve integration of neural communication in the central nervous system.

Animals↗
PubMed1995

Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.

Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been recently implicated to have a functional role in a number of other reproductive events. The physiological effects of progesterone are mediated by the progesterone receptor (PR), a member of the nuclear receptor superfamily of transcription factors. In most cases the PR is induced by estrogen, implying that many of the in vivo effects attributed to progesterone could also be the result of concomitantly administered estrogen. Therefore, to clearly define those physiological events that are specifically attributable to progesterone in vivo, we have generated a mouse model carrying a null mutation of the PR gene using embryonic stem cell/gene targeting techniques. Male and female embryos homozygous for the PR mutation developed normally to adulthood. However, the adult female PR mutant displayed significant defects in all reproductive tissues. These included an inability to ovulate, uterine hyperplasia and inflammation, severely limited mammary gland development, and an inability to exhibit sexual behavior. Collectively, these results provide direct support for progesterone's role as a pleiotropic coordinator of diverse reproductive events that together ensure species survival.

Animals↗
PubMed1994

Convergent pathways for steroid hormone- and neurotransmitter-induced rat sexual behavior.

Estrogen and progesterone modulate gene expression in rodents by activation of intracellular receptors in the hypothalamus, which regulate neuronal networks that control female sexual behavior. However, the neurotransmitter dopamine has been shown to activate certain steroid receptors in a ligand-independent manner. A dopamine receptor stimulant and a D1 receptor agonist, but not a D2 receptor agonist, mimicked the effects of progesterone in facilitating sexual behavior in female rats. The facilitory effect of the neurotransmitter was blocked by progesterone receptor antagonists, a D1 receptor antagonist, or antisense oligonucleotides to the progesterone receptor. The results suggest that in rodents neurotransmitters may regulate in vivo gene expression and behavior by means of cross-talk with steroid receptors in the brain.

Adrenal Glands↗
PubMed1994

Nitric oxide mediates sexual behavior in female rats.

Nitric oxide (NO), an active free radical formed during the conversion of arginine to citrulline by the enzyme NO synthase (NOS), mediates vasorelaxation, cytotoxicity, and neurotransmission. Neurons containing NOS (NOergic) are located in the hypothalamus. These NOergic neurons control the release of several hypothalamic peptides. Release of NO from these NOergic neurons stimulates pulsatile release of luteinizing hormone-releasing hormone (LHRH) in vivo and LHRH release in vitro. LHRH not only induces LH release, which induces ovulation, but also facilitates female sexual behavior. Sexual behavior can be induced reliably in estrogen-primed ovariectomized female rats by progesterone (P). This behavior consists of proceptive behavior to attract the male and the assumption of a clear characteristic posture, lordosis, when mounted by the male. To ascertain the role of NO in the control of sexual behavior in female rats, an inhibitor of NOS, NG-monomethyl-L-arginine was microinjected into the third cerebral ventricle (3V) of conscious, ovariectomized, estrogen-primed rats with indwelling cannulae. NG-Monomethyl-L-arginine (10-1000 micrograms) prevented P-facilitated lordosis when administered intracerebroventricularly into the 3V, 20 min prior to the 3V injection of P. NG-Monomethyl-D-arginine, which does not inhibit NOS, did not inhibit lordosis under the same experimental conditions. Microinjection into the 3V of sodium nitroprusside (SNP), which spontaneously releases NO, facilitated lordosis in estrogen-primed rats in the absence of P. The facilitation of lordosis induced by either P or SNP was prevented by intracerebroventricular injection of hemoglobin, which binds NO. Lordosis facilitated by P or SNP was blocked by injection of LHRH antiserum into the 3V. The results are interpreted to mean that the P-facilitated lordosis response is mediated by LHRH release. Furthermore, since NO release from SNP also facilitates lordosis in the absence of P and this response could be blocked by LHRH antiserum, we conclude that P brings about the release of NO, which stimulates LHRH release that facilitates lordosis. Thus, the results indicate that NO induces LHRH release and that LHRH then plays a crucial role in mediation of sexual behavior in the female rats.

Amino Acid Oxidoreductases↗
PubMed1994

Inhibition of rat sexual behavior by antisense oligonucleotides to the progesterone receptor.

To test further the idea that sexual behavior in rodents is mediated via the progesterone receptor (PR) in the ventromedial nucleus of the hypothalamus, antisense and sense oligonucleotides to progesterone receptor were administered intracerebroventricularly into the third cerebral ventricle of ovariectomized estrogen-primed animals. Progesterone-facilitated sexual behavior was inhibited in animals treated with antisense oligonucleotides, with proceptive and receptive responses being minimal or completely suppressed. Sexual behavior was not altered by control sense oligonucleotides. In vitro binding assays of the cytosol progesterone receptors demonstrated a 52.2% reduction of PRs in the hypothalamus of animals that received antisense oligonucleotides, suggesting a reduction in PR synthesis. These data suggest that a threshold level of estrogen-induced hypothalamic PR is critical in the regulation of progesterone-facilitated sexual behavior in female rats.

Animals↗
PubMed1992

Initiation and maintenance of in vitro decidualization are independent of hormonal sensitization in vivo.

The effects of in vivo hormonal sensitization on the competence of uterine stromal (US) cells to decidualize in vitro were assessed. In vitro differentiation of uterine stroma isolated from Day 4 pregnant rats, sensitized to respond to a decidual stimulus, was compared to that in nonsensitized immature, castrated or cycling rats. The initiation of in vitro decidualization--as monitored by the expression of the decidual markers desmin and laminin in rat US cells--was independent of the hormonal status of the animal from which the cells were isolated and occurred in the absence of serum in the medium. Differentiation was accelerated in high-density cultures where contact inhibition suppressed proliferation and decreased the extent of cell growth. The extent to which in vitro decidualization imitates in vivo stromal cell differentiation was assessed by comparing decidualization in the rabbit, a species with only a limited decidual cell response, and in the rat. US cells isolated from nonpregnant rabbits differentiated in vitro by expressing laminin, but not desmin. Indirect immunofluorescence of frozen uterine sections from pregnant and nonpregnant rabbits validated in vitro differentiation as a faithful reflection of the in vivo program of decidualization. Although the program of US cell differentiation may vary between the species, initiation of differentiation in vitro appeared to be independent of hormonal preparation in vivo for both the species examined.

Animals↗
PubMed1992

Steroid hormones differentially modulate glycoconjugate synthesis and vectorial secretion by polarized uterine epithelial cells in vitro.

Characterization of glycoconjugates synthesized by polarized immature rabbit uterine epithelial (UE) cells in vitro, their vectorial patterns of secretion, and regulation by ovarian steroid hormones are reported. Large (mol wt, greater than 230 kDa) sialomucoglycoproteins and hyaluronate were primarily (86-96%) secreted from the apical cell surface domain, while heparan sulfate proteoglycans were predominantly secreted from the basal cell surface of the polarized UE cells. The polarized UE cells responded to estrogen and progesterone in vitro and exhibited distinct profiles in their synthesis and secretion of different glycoconjugates. Progesterone and/or estrogen reduced the secretion of the mucosialoglycoproteins; however, progesterone caused a 4- to 5-fold accumulation of mucosialoglycoproteins in the cell-associated fraction, suggesting regulation by the hormone at the level of secretion, rather than synthesis. Estrogen and progesterone both stimulated the synthesis and secretion of hyaluronate by the polarized UE cells. Neither hormone substantially altered the synthesis or secretory pattern of heparan sulfate proteoglycans. Collectively, these studies provide the first comprehensive characterization of the major glycoconjugates synthesized and secreted by rabbit UE cells. Furthermore, these observations demonstrate marked differential direct influences of steroid hormones on the production of distinct classes of UE cell glycoconjugates.

Animals↗
PubMed1991

Dopaminergic and ligand-independent activation of steroid hormone receptors.

The current view of how steroid hormone receptors affect gene transcription is that these receptors, on binding ligand, change to a state in which they can interact with chromatin and regulate transcription of target genes. Receptor activation is believed to be dependent only on this ligand-binding event. Selected steroid hormone receptors can be activated in a ligand-independent manner by a membrane receptor agonist, the neurotransmitter dopamine. In vitro, dopamine faithfully mimicked the effect of progesterone by causing a translocation of chicken progesterone receptor (cPR) from cytoplasm to nucleus. Dual activation by progesterone and dopamine was dissociable, and a serine residue in the cPR was identified that is not necessary for progesterone-dependent activation of cPR, but is essential for dopamine activation of this receptor.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Hormonal responsiveness by immature rabbit uterine epithelial cells polarized in vitro.

This paper reports the development of an in vitro cell culture system of polarized uterine epithelial (UE) cells from the immature rabbit. UE cells from immature rabbit were cultured on EHS (Engelbreth-Holm-Swarm) matrix-coated semipermeable filter inserts in a serum-free, phenol red-free defined medium. The cells in primary culture attached, proliferated, formed monolayers, and exhibited structural and functional polarity. Structural differentiation was validated by ultrastructural features, such as apical microvilli, intercellular junctions, desmosomes, and polar organization of apical vs. basal membrane domains. Trans-monolayer epithelial resistance, a reflection of functional tight junctions, preferential basal uptake of [35S]methionine, polarized distribution of labeled secretory proteins, and increased secretory activity marked by preferential apical secretion (greater than 90%) of proteins were indices of functional polarity. With the development and maintenance of polarized state by the UE cells, some of the newly synthesized proteins were sorted and vectorially secreted into their distinct compartments. De novo synthesis and exclusive apical secretion of uteroglobin (a progesterone-induced protein in vivo) by the polarized UE cells occurred in response to progesterone treatment in vitro. The hormone responsiveness was maintained for a prolonged period under these conditions. A culture system in which the UE cells maintain functional and morphological polarity and sustain their hormonal responsiveness facilitates the study of regulation of specialized functions by the UE cells that are regulated by steroid hormones and their interactions with the other uterine cell types.

Animals↗
PubMed1988

Servomechanism of prolactin and progesterone in regulating uterine gene expression.

To investigate the interaction of PRL and progesterone in regulating uterine gene expression, we have quantitated the concentration of PRL receptor and of uteroglobin (UG) mRNA in the endometrium of rabbits of different ages and after treatment with different hormones. During uterine differentiation in 2- to 4-week old rabbits, a marked increase in unoccupied uterine PRL receptor number was observed, presumably increasing uterine sensitivity to PRL. Receptor values for 4-week old rabbits were comparable to values for sexually mature, estrous females, but were lower than in 5-day pseudopregnant (PSP) animals. When total PRL receptor was determined by Scatchard analysis after in vitro desaturation with MgCl2, PSP animals again expressed the highest receptor concentration with no changes in the dissociation constant (Kd) values. To determine whether progesterone regulates uterine PRL receptor, long term ovariectomized rabbits (greater than 12 weeks) were treated with various combinations of hormones, and unoccupied and total uterine PRL receptors were determined. Progesterone treatment resulted in the highest concentration of both unoccupied and total PRL receptor after desaturation and removal of anti-ovine PRL antibodies with MgCl2. The value for total uterine PRL receptor was equivalent to the value for mammary gland, and the Kd values (2-4 x 10(-10) M) were similar. Treatment of long term ovariectomized rabbits with progesterone, with or without estradiol, produced an increase (P less than 0.05) in the UG mRNA content, which also occurred in PSP animals. PRL alone had no effect on UG mRNA but PRL plus progesterone increased (P less than 0.05) UG mRNA in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗