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Results for “hormone cross talk”

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At least 19 recordsLinked to original sources
PubMed1993

Formation of retinoid X receptor homodimers leads to repression of T3 response: hormonal cross talk by ligand-induced squelching.

Thyroid hormone receptors (TRs) form heterodimers with retinoid X receptors (RXRs). Heterodimerization is required for efficient TR DNA binding to most response elements and transcriptional activation by thyroid hormone. RXRs also function as auxiliary proteins for several other receptors. In addition, RXR alpha can be induced by specific ligands to form homodimers. Here we report that RXR-specific retinoids that induce RXR homodimers are effective repressors of the T3 response. We provide evidence that this repression by RXR-specific ligands occurs by sequestering of RXR from TR-RXR heterodimers into RXR homodimers. This ligand-induced squelching may represent an important mechanism by which RXR-specific retinoids and 9-cis retinoic acid mediate hormonal cross talk among a subfamily of nuclear receptors activated by structurally unrelated ligands.

Animals↗
PubMedDate not supplied

Hormonal cross talk in insect development.

Two hormones, 20-hydroxyecdysone (20E) and juvenile hormone (JH), coordinately orchestrate insect growth and development. 20E initiates all major developmental transitions from egg, to larva, to pupa, to adult, but it is an interaction with the JH signal that transduces 20E pulses into stage-specific responses. Years of research have given us an understanding of 20E signaling pathway. By contrast, the molecular mechanism of JH action remains an enigma. Recent studies provide insight into the molecular background to JH-20E regulatory interplay. Two transcription factors--BR-C and E75A--contribute to the cross-talk between the two hormones. It appears that BR-C is a key target of JH status quo action, and E75A is a part of the mechanism whereby JH prevents BR-C activation.

Animals↗
PubMed2005

Cross talk in hormonally regulated gene transcription through induction of estrogen receptor ubiquitylation.

Estrogen tightly regulates the levels of circulating gonadotropins, but a direct effect of estrogen receptor alpha (ERalpha) on the mammalian LHbeta gene has remained poorly defined. We demonstrate here that ERalpha can associate with the LHbeta promoter through interactions with Sf-1 and Pitx1 without requiring an estrogen response element (ERE). We show that gonadotropin-releasing hormone (GnRH) promotes ERalpha ubiquitylation and also degradation while stimulating expression of ubc4. GnRH also increases the association and lengthens the cycling time of ERalpha on the LHbeta promoter. The ERalpha association and transactivation of the LHbeta gene, as well as ERalpha degradation, are increased following ubc4 overexpression, while the effects of GnRH are abated following ubc4 knockdown. Our results indicate that ERalpha ubiquitylation and subsequent transactivation of the LHbeta gene can be induced by increasing the levels of the E2 enzyme as a result of signaling by an extracellular hormone, thus providing a new form of cross talk in hormonally stimulated regulation of gene expression.

Animals↗
PubMed2003

Cross-talk in plant hormone signalling: what Arabidopsis mutants are telling us.

Genetic screens have been extremely useful in identifying genes involved in hormone signal transduction. However, although these screens were originally designed to identify specific components involved in early hormone signalling, mutations in these genes often confer changes in sensitivity to more than one hormone at the whole-plant level. Moreover, a variety of hormone response genes has been identified through screens that were originally designed to uncover regulators of sugar metabolism. Together, these facts indicate that the linear representation of the hormone signalling pathways controlling a specific aspect of plant growth and development is not sufficient, and that hormones interact with each other and with a variety of developmental and metabolic signals. Following the advent of arabidopsis molecular genetics we are beginning to understand some of the mechanisms by which a hormone is transduced into a cellular response. In this Botanical Briefing we review a subset of genes in arabidopsis that influence hormonal cross-talk, with emphasis on the gibberellin, abscisic acid and ethylene pathways. In some cases it appears that modulation of hormone sensitivity can cause changes in the synthesis of an unrelated hormone, while in other cases a hormone response gene defines a node of interaction between two response pathways. It also appears that a variety of hormones may converge to regulate the turnover of important regulators involved in growth and development. Examples are cited of the recent use of suppressor and enhancer analysis to identify new nodes of interaction between these pathways.

Abscisic Acid↗
PubMed2000

Hormonal cross-talk between auxin and ethylene differentially regulates the expression of two members of the 1-aminocyclopropane-1-carboxylate oxidase gene family in rice (Oryza sativa L.).

Two cDNA clones, pOS-ACO2 and pOS-ACO3, encoding 1-aminocyclopropane-1-carboxylate (ACC) oxidase were isolated from rice seedling cDNA library. pOS-ACO3 is a 1,299 bp full-length clone encoding 321 amino acids (Mr=35.9 kDa), while pOS-ACO2 is 1,072 bp long and is a partial cDNA clone encoding 314 amino acids. These two deduced amino acid sequences share 70% identity, and display a high degree of sequence identity (72-92%) with previously isolated pOS-ACO1 of deepwater rice. The chromosomal location studies show that OS-ACO2 is positioned on the long arm of chromosome 9, while OS-ACO3 on the long arm of chromosome 2 of rice genome. A marked increase in the level of OS-ACO2 transcript was observed in IAA-treated etiolated rice seedlings, whereas the OS-ACO3 mRNA was greatly accumulated by ethylene treatment. Results of ethylene inhibitor studies indicated that auxin promotion of the OS-ACO2 transcription was not mediated through the action of auxin-induced ethylene. Thus, it appears that there are two groups of ACC oxidase transcripts in rice plants, either auxin-induced or ethylene-induced. The auxin-induced OS-ACO2 expression was partially inhibited by ethylene, while ethylene induction of OS-ACO3 transcription was completely blocked by auxin. These results indicate that the expression of ACC oxidase genes is regulated by complex hormonal networks in a gene specific manner in rice seedlings. Okadaic acid, a potent inhibitor of protein phosphatase, effectively suppressed the IAA induction of OS-ACO2 expression, suggesting that protein dephosphorylation plays a role in the induction of ACC oxidase by auxin. A scheme of the multiple regulatory pathways for the expression of ACC oxidase gene family by auxin, ethylene and protein phosphatase is presented.

Amino Acid Oxidoreductases↗
PubMed1996

Thioredoxin: a redox-regulating cellular cofactor for glucocorticoid hormone action. Cross talk between endocrine control of stress response and cellular antioxidant defense system.

Adaptation to stress evokes a variety of biological responses, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and synthesis of a panel of stress-response proteins at cellular levels: for example, expression of thioredoxin (TRX) is significantly induced under oxidative conditions. Glucocorticoids, as a peripheral effector of the HPA axis, exert their actions via interaction with a ligand-inducible transcription factor glucocorticoid receptor (GR). However, how these stress responses coordinately regulate cellular metabolism is still unknown. In this study, we demonstrated that either antisense TRX expression or cellular treatment with H2O2 negatively modulates GR function and decreases glucocorticoid-inducible gene expression. Impaired cellular response to glucocorticoids is rescued by overexpression of TRX, most possibly through the functional replenishment of the GR. Moreover, not only the ligand binding domain but the DNA binding domain of the GR is also suggested to be a direct target of TRX. Together, we here present evidence showing that cellular glucocorticoid responsiveness is coordinately modulated by redox state and TRX level and propose that cross talk between neuroendocrine control of stress responses and cellular antioxidant systems may be essential for mammalian adaptation processes.

Animals↗
PubMed2003

Making sense of cross-talk between steroid hormone receptors and intracellular signaling pathways: who will have the last word?

In classical models of nuclear steroid hormone receptor function, ligand binds receptor, heat shock proteins dissociate, and receptor dimers enter or are withheld in the nucleus and interact with coregulatory molecules to mediate changes in gene expression. The footnotes, "receptors become phosphorylated" and "dynamic nucleo-cytoplasmic shuttling occurs" describe well-accepted, but less well-understood aspects of receptor action. Recently, the idea that several protein kinases are activated in response to steroid hormone binding to cognate cytoplasmic or membrane-associated receptors has become fashionable. However, the precise role of steroid hormone receptor phosphorylation and our understanding of which cytoplasmic kinases are activated and their functional significance remain elusive. This review provides an overview of the primary ways in which steroid hormone receptor and growth factor cross-talk occurs, using the human progesterone receptor (PR) as a model. The functional consequences of PR phosphorylation by protein kinases classically activated in response to peptide growth factors and novel extranuclear or nongenomic functions of PR as potential independent initiators of signal transduction pathways are discussed. Intracellular protein kinases are emerging as key mediators of steroid hormone receptor action. Cross-talk between steroid receptor- and growth factor-initiated signaling events may explain how gene subsets are coordinately regulated by mitogenic stimuli in hormonally responsive normal tissues, and is suspected to play a role in their cancer biology.

Animals↗
PubMed1995

Inhibitory cross-talk between steroid hormone receptors: differential targeting of estrogen receptor in the repression of its transcriptional activity by agonist- and antagonist-occupied progestin receptors.

Although estrogen receptor (ER) and progestin receptor (PR) are members of different steroid hormone receptor subfamilies, there is considerable biological evidence for cross-talk between the estrogen and progestin hormone-receptor signaling pathways. We have developed a model system to analyze the mechanisms underlying this cross-talk, specifically the repression of ER-mediated transcriptional activity by PR complexed with agonistic or antagonistic ligands. Estrogen- and progestin-responsive reporter vectors containing a variety of promoters were transfected into primary cultures of rat uterine cells and 3T3 mouse fibroblasts with expression vectors for PR (the A and/or B isoforms) as well as ER. Our results demonstrate that both PR isoforms can act as potent ligand-dependent repressors of ER activity. The magnitude of the repression was dependent on the PR isoform (i.e., PR A or PR B), ligand type (i.e., agonist or antagonist), PR levels, and ligand concentration but was unaffected by the ER levels. The promoter context was important in determining both the magnitude and PR isoform specificity of the repression for agonist-occupied PR but not for antagonist-occupied PR. Ligand-occupied PR A was a stronger repressor of ER-mediated transcriptional activity than was ligand-occupied PR B, and antagonist-occupied PR was a more effective repressor than agonist-occupied PR. Mechanistic studies suggest that liganded PR represses ER activity by interfering with its ability to interact productively with the transcriptional machinery, a process known as quenching. The data do not support competitive repression, direct repression, or squelching as the mechanism of PR's inhibitory effect. Experiments with ER mutants demonstrated that the N-terminal portion of ER was required for repression by agonist-occupied PR but not by antagonist-occupied PR. These results, as well as other differences between the two PR-ligand complexes, suggest that they differentially target ER when repressing ER transcriptional activity. These findings underscore the mounting evidence for the importance of interactions between members of the steroid hormone receptor family.

3T3 Cells↗
PubMed2002

Regulation of androgen receptor mRNA expression in primary culture of Harderian gland cells: cross-talk between steroid hormones.

The androgen receptor (AR) must be considered a transcription factor belonging to the steroid-thyroid hormones receptor superfamily. Previous results gained from the Harderian gland, a tubulo-alveolar gland located in the orbital cavity of the golden hamster, indicate that Harderian gland cells express mRNAs encoding for androgen, glucocorticoid, thyroid hormone (T(3)), and estrogen receptors, respectively. Since in other systems, these receptors have been related to the expression of the androgen receptor, we have studied the regulation of AR expression in primary cultures of the male hamster Harderian gland. Our in vitro experiments show that androgen, and thyroid hormones increase the expression of AR. Retinoic acids also show a positive effect on AR expression, while exposure to glucocorticoid or estrogen blocks AR expression. Since these steroids differently modulate AR expression, our results must be considered in the context of multi-hormonal control of gene expression that could act through cross-talk between members of the steroid-thyroid hormones.

Animals↗
PubMed1997

The transcriptional integrator CREB-binding protein mediates positive cross talk between nuclear hormone receptors and the hematopoietic bZip protein p45/NF-E2.

Thyroid hormone (T3) and retinoic acid (RA) play important roles in erythropoiesis. We found that the hematopoietic cell-specific bZip protein p45/NF-E2 interacts with T3 receptor (TR) and RA receptor (RAR) but not retinoid X receptor. The interaction is between the DNA-binding domain of the nuclear receptor and the leucine zipper region of p45/NF-E2 but is markedly enhanced by cognate ligand. Remarkably, ligand-dependent transactivation by TR and RAR is markedly potentiated by p45/NF-E2. This effect of p45/NF-E2 is prevented by maf-like protein p18, which functions positively as a heterodimer with p45/NF-E2 on DNA. Potentiation of hormone action by p45/NF-E2 requires its activation domain, which interacts strongly with the multifaceted coactivator cyclic AMP response element protein-binding protein (CBP). The region of CBP which interacts with p45/NF-E2 is the same interaction domain that mediates inhibition of hormone-stimulated transcription by AP1 transcription factors. Overexpression of the bZip interaction domain of CBP specifically abolishes the positive cross talk between TR and p45/NF-E2. Thus, positive cross talk between p45/NF-E2 and nuclear hormone receptors requires direct protein-protein interactions between these factors and with CBP, whose integration of positive signals from two transactivation domains provides a novel mechanism for potentiation of hormone action in hematopoietic cells.

Animals↗
PubMed2006

Molecular mechanisms of cross-talk between thyroid hormone and peroxisome proliferator activated receptors: focus on the heart.

Thyroid hormone receptors (TR) and peroxisome proliferator activated receptors (PPAR) regulate cardiac metabolism. Numerous studies have examined TR and PPAR function since PPAR was first discovered in the early 1990s, however few have evaluated TR and PPAR interactions. Although ligands for these members of the nuclear steroid receptor family are under evaluation for treatment of congestive heart failure and various metabolic diseases, their interactions have not been investigated in detail in heart. These interactions are remarkably complicated. Nevertheless, their identification and elucidation is extremely important for further development of specific drugs. We review here the fundamental ways TRs and PPARs are regulated and how their cross-talk patterns mediate transcription of their target genes.

Animals↗
PubMed2005

Cross-talk between thyroid hormone receptor and liver X receptor regulatory pathways is revealed in a thyroid hormone resistance mouse model.

Hypercholesterolemia is found in patients with hypothyroidism and resistance to thyroid hormone. In this study, we examined cholesterol metabolism in a thyroid hormone receptor beta (TR-beta) mutant mouse model of resistance to thyroid hormone. Whereas studies of cholesterol metabolism have been reported in TR-beta knock-out mice, generalized expression of a non-ligand binding TR-beta protein in this knock-in model more fully recapitulates the hypothyroid state, because the hypothyroid effect of TRs is mediated by the unliganded receptor. In the hypothyroid state, a high cholesterol diet increased serum cholesterol levels in wild-type animals (WT) but either did not change or reduced levels in mutant (MUT) mice relative to hypothyroidism alone. 7alpha-Hydroxylase (CYP7A1) is the rate-limiting enzyme in cholesterol metabolism and mRNA levels were undetectable in the hypothyroid state in all animals. triiodothyronine replacement restored CYP7A1 mRNA levels in WT mice but had minimal effect in MUT mice. In contrast, a high cholesterol diet markedly induced CYP7A1 levels in MUT but not WT mice in the hypothyroid state. Elevation of CYP7A1 mRNA levels and reduced hepatic cholesterol content in MUT animals are likely because of cross-talk between TR-beta and liver X receptor alpha (LXR-alpha), which both bind to a direct repeat + 4 (DR+4) element in the CYP7A1 promoter. In transfection studies, WT but not MUT TR-beta antagonized induction of this promoter by LXR-alpha. Electromobility shift analysis revealed that LXR/RXR heterodimers bound to the DR+4 element in the presence of MUT but not WT TR-beta. A mechanism for cross-talk, and potential antagonism, between TR-beta and LXR-alpha is proposed.

Animals↗
PubMed1996

Cross-talk between thyroid hormone and specific retinoid X receptor subtypes in yeast selectively regulates cognate ligand actions.

Thyroid (T3) hormone beta1 (TR) and 9-cis retinoic acid (9c-RA) retinoid X receptors (RXR) can form heterodimer complexes that bind to hormone response elements (HREs) in target genes to either activate or repress transcription. However, the action of each cognate ligand and the accessory cellular factors that can differentially regulate the transcriptional responses of a heterodimer-DNA complex are not well understood. Studies in most mammalian cell lines have demonstrated that 9c-RA cannot bind or transactivate TR/RXR-T3 response element (TRE) complexes. In contrast, when identical heterodimer complexes were coexpressed in the yeast (Saccharomyces cerevisiae) with single copy typical TREs [i.e., DR+4 (direct repeat), F2 (everted repeat), or PAL (inverted repeat) DNA response elements] we observed that i) unliganded TRbeta1 homodimers had constitutive action on F2 and PAL but not DR4 TREs; ii) TRbeta1 homodimer responsivity to T3 ligand was relatively weak (less than twofold) and was only demonstrable on F2 but not PAL or DR4-TREs, whereas TRbeta1 heterodimers responded to T3 when RXRgamma but not RXR alpha was the heterodimeric partner; iii) RXR responsivity to 9c-RA (three- to sixfold) could be demonstrated only on palindromic TREs that could be enhanced by TRbeta1 on all TREs; iv) T3 + 9c-RA ligands increased (additively or synergistically) transactivation when RXRgamma but not alpha heterodimerized with TRbeta1 on both typical as well as atypical (DR1, DR3, DR5, and F2M) TREs. Substitutions for wild-type TRbeta1 of C-terminus mutants deficient in dimerization with RXRs abrogated the anticipated single and dual cognate ligand-induced effects on TRbeta1/RXRgamma transactivation of DR4 TREs, whereas mutants with preserved dimerization function but impaired T3 transactivation regions could maintain an enhanced 9c-RA response but were devoid of the anticipated T3 and dual (T3 + 9c-RA) cognate ligand-induced effects. Thus, the ligand-inducible response of TR and RXR homodimers expressed in yeast are relatively weak but can be further enhanced by TRbeta1 cross-talk with specific RXR subtypes in the presence of both cognate ligands.

Animals↗
PubMed2002

A conditionally fertile coi1 allele indicates cross-talk between plant hormone signalling pathways in Arabidopsis thaliana seeds and young seedlings.

Jasmonates (JAs) regulate Arabidopsis thaliana (L.) Heynh. wound and defense responses, pollen development, and stress-related growth inhibition. Significantly, each of these responses requires COI1, an F-box protein. We fused firefly luciferase as a reporter to the JA-responsive promoter for the vegetative storage protein gene (VSP) and used this to screen for mutants that failed to express luciferase in the presence of JA, isolating a mutant designated coi1-16. Comparisons with coi1-1 and jar1-1 plants indicated that coi1-16 was only slightly more sensitive to JA than coi1-1 plants. However, whilst coi1-16 plants failed to produce viable pollen at 22 degrees C, they were fertile at 16 degrees C. Therefore, unlike the other coi1 mutants, coi1-16 could be maintained as a pure line and did not require selection. We have used coi1-16 seeds to define novel interactions between JA and other hormone signalling pathways in seed germination and in the development of young seedlings.

Abscisic Acid↗
PubMed1995

Peroxisome proliferator-activated receptor mediates cross-talk with thyroid hormone receptor by competition for retinoid X receptor. Possible role of a leucine zipper-like heptad repeat.

The peroxisome proliferator-activated receptors (PPAR) and thyroid hormone receptors (TR) are members of the nuclear receptor superfamily, which regulate lipid metabolism and tissue differentiation. In order to bind to DNA and activate transcription, PPAR requires the formation of heterodimers with the retinoid X receptor (RXR). In addition to activating transcription through its own response elements, PPAR is able to selectively down-regulate the transcriptional activity of TR, but not vitamin D receptor. The molecular basis of this functional interaction has not been fully elucidated. By means of site-directed mutagenesis of hPPAR alpha we mapped its inhibitory action on TR to a leucine zipper-like motif in the ligand binding domain of PPAR, which is highly conserved among all subtypes of this receptor and mediates heterodimerization with RXR. Replacement of a single leucine by arginine at position 433 of hPPAR alpha (L433R) abolished heterodimerization of PPAR with RXR and consequently its trans-activating capacity. However, a similar mutation of a leucine residue to arginine at position 422 showed no alteration of heterodimerization, DNA binding, or transcriptional activation. The dimerization deficient mutant L433R was no longer able to inhibit TR action, demonstrating that the selective inhibitory effect of PPAR results from the competition for RXR as well as possibly for other TR-auxiliary proteins. In contrast, abolition of DNA binding by a mutation in the P-box of PPAR (C122S) did not eliminate the inhibition of TR trans-activation, indicating that competition for DNA binding is not involved. Additionally, no evidence for the formation of PPAR:TR heterodimers was found in co-immunoprecipitation experiments. In summary, we have demonstrated that PPAR selectively inhibits the transcriptional activity of TRs by competition for RXR and possibly non-RXR TR-auxiliary proteins. In contrast, this functional interaction is independent of the formation of PPAR:TR heterodimers or competition for DNA binding.

Amino Acid Sequence↗
PubMed2006

Differential mechanisms for PACAP and GnRH cAMP induction contribute to cross-talk between both hormones in the gonadotrope LbetaT2 cell line.

The effects and respective influence of pituitary adenylate cyclase-activating polypeptide (PACAP) and gonadotropin-releasing hormone (GnRH) on cyclic AMP (cAMP) production in pituitary gonadotropes were analyzed using the LbetaT2 cell line. Both hormones induced cAMP with, however, different intensity and time course. In addition, the GnRH effect was markedly reduced by PKC inhibitors. Despite its positive coupling to cAMP pathway, GnRH counteracted PACAP induction of cAMP and this effect was mimicked by the PKC activator phorbol 12-myristate 13-acetate (PMA). The data reveal major differences in the mechanisms by which PACAP and GnRH activate cAMP/PKA pathway in LbetaT2 cells and suggest that PKC activation serves GnRH not only to increase cAMP but also to counteract the PACAP stimulation of this signaling pathway.

Animals↗
PubMed2005

Transcriptional modulations by RXR agonists are only partially subordinated to PPARalpha signaling and attest additional, organ-specific, molecular cross-talks.

Nuclear hormone receptors (NR) are important transcriptional regulators of numerous genes involved in diverse pathophysiological and therapeutic functions. Following ligand activation, class II NR share the ability to heterodimerize with the retinoid X receptor (RXR). It is established that RXR activators, rexinoids, transactivate several peroxisome proliferator-activated receptor alpha (PPARalpha) target genes in a PPARalpha-dependent manner. We hypothesized that, once activated, RXR might signal through quiescent NR other than PPARalpha, in an organ-specific manner. To study this putative phenomenon in vivo, we developed an array of 120 genes relevant to the class II NR field. The genes were selected using both published data and high-density screenings performed on RXR or PPARalpha agonist-treated mice. Wild-type C57BL/6J and PPARalpha-deficient mice were treated with fenofibrate (PPARalpha activator) or LGD1069 (RXR activator). Using our customized array, we studied the hepatic, cardiac, and renal expression of this panel of 120 genes and compared them in both murine genotypes. The results obtained from this study confirmed the ability of an RXR agonist to modulate PPARalpha-restricted target genes in the liver and the kidney. Furthermore, we show that various organ-specific regulations occurring in both genotypes (PPARalpha +/+ or -/-) are highly indicative of the ability of RXR to recruit other class II NR pathways. Further development of this molecular tool may lead to a better understanding of the permissiveness of class II nuclear receptor dimers in vivo.

Animals↗