Gene Symbol: pomca
Description: proopiomelanocortin a
Alias: ACTH, MSH, SI:bZ36D5.1, SI:bZ36D5.4, pomc, si:bz36d5.2, pro-opiomelanocortin, beta-endorphin
Species: zebrafish

Top Publications

  1. Hansen I, To T, Wortmann S, Burmester T, Winkler C, Meyer S, et al. The pro-opiomelanocortin gene of the zebrafish (Danio rerio). Biochem Biophys Res Commun. 2003;303:1121-8 pubmed
    ..from the coding region while intron 2 (1522 bp) is located between the signal peptide and the sequence encoding ACTH. Transcription starts 26 bp downstream of a TATA box and there is one polyadenylation signal in the 3(') ..
  2. Alderman S, Bernier N. Ontogeny of the corticotropin-releasing factor system in zebrafish. Gen Comp Endocrinol. 2009;164:61-9 pubmed publisher
    ..Overall, results from this study establish the zebrafish as a model species for research on stress during ontogeny and offer new insights into an HPI-axis independent function for the CRF system during embryogenesis. ..
  3. Fuzzen M, Van der Kraak G, Bernier N. Stirring up new ideas about the regulation of the hypothalamic-pituitary-interrenal axis in zebrafish (Danio rerio). Zebrafish. 2010;7:349-58 pubmed publisher
    ..These findings suggest that multiple genes at all levels of the HPI axis play an active role in the stimulation and termination of the cortisol stress response in zebrafish. ..
  4. Nica G, Herzog W, Sonntag C, Hammerschmidt M. Zebrafish pit1 mutants lack three pituitary cell types and develop severe dwarfism. Mol Endocrinol. 2004;18:1196-209 pubmed
    ..as in the mouse, expression is restricted to a subset of pituitary cell types, excluding proopiomelanocortin (pomc)-expressing cells (corticotropes, melanotropes) and possibly gonadotropes...
  5. Nica G, Herzog W, Sonntag C, Nowak M, Schwarz H, Zapata A, et al. Eya1 is required for lineage-specific differentiation, but not for cell survival in the zebrafish adenohypophysis. Dev Biol. 2006;292:189-204 pubmed
    ..Eya1 is required for lineage-specific differentiation of adenohypophyseal cells, but not for their survival, thereby uncoupling the differentiation-promoting and anti-apoptotic effects of Eya proteins seen in other tissues. ..
  6. Griffiths B, Schoonheim P, Ziv L, Voelker L, Baier H, Gahtan E. A zebrafish model of glucocorticoid resistance shows serotonergic modulation of the stress response. Front Behav Neurosci. 2012;6:68 pubmed publisher
    ..post-fertilization, mutant larvae had elevated whole body cortisol, increased expression of pro-opiomelanocortin (POMC), the precursor of adrenocorticotropic hormone (ACTH), and failed to show normal suppression of stress markers ..
  7. Liu F, Pogoda H, Pearson C, Ohyama K, L hr H, Hammerschmidt M, et al. Direct and indirect roles of Fgf3 and Fgf10 in innervation and vascularisation of the vertebrate hypothalamic neurohypophysis. Development. 2013;140:1111-22 pubmed publisher
    ..Together, our studies suggest a model for the integrated neurohemal wiring of the hypothalamo-neurohypophyseal axis...
  8. Herzog W, Sonntag C, von der Hardt S, Roehl H, Varga Z, Hammerschmidt M. Fgf3 signaling from the ventral diencephalon is required for early specification and subsequent survival of the zebrafish adenohypophysis. Development. 2004;131:3681-92 pubmed
    ..This early specification seems to be essential for the subsequent survival of pituitary cells, but not for pituitary morphogenesis or pituitary cell proliferation...
  9. Herzog W, Sonntag C, Walderich B, Odenthal J, Maischein H, Hammerschmidt M. Genetic analysis of adenohypophysis formation in zebrafish. Mol Endocrinol. 2004;18:1185-95 pubmed
    ..Positional cloning of the lia, pia, and aal genes might reveal novel regulators of vertebrate pituitary development. ..

More Information


  1. Pogoda H, von der Hardt S, Herzog W, Kramer C, Schwarz H, Hammerschmidt M. The proneural gene ascl1a is required for endocrine differentiation and cell survival in the zebrafish adenohypophysis. Development. 2006;133:1079-89 pubmed
    ..Together, this suggests that Ascl1a might act downstream of diencephalic Fgf3 signaling to mediate some of the effects of Fgf3 on the developing adenohypophysis...
  2. Dickmeis T, Lahiri K, Nica G, Vallone D, Santoriello C, Neumann C, et al. Glucocorticoids play a key role in circadian cell cycle rhythms. PLoS Biol. 2007;5:e78 pubmed
    ..Instead, they act in concert with a systemic signaling environment of which glucocorticoids are an essential part. ..
  3. Lin J, Hu S, Ho P, Hsu H, Postlethwait J, Chung B. Two Zebrafish hsd3b Genes Are Distinct in Function, Expression, and Evolution. Endocrinology. 2015;156:2854-62 pubmed publisher
    ..Zebrafish hsd3b1(Dre 9), on the contrary, functions like mammalian HSD3B2, whose deficiency leads to congenital adrenal hyperplasia. ..
  4. Dutta S, Dietrich J, Aspöck G, Burdine R, Schier A, Westerfield M, et al. pitx3 defines an equivalence domain for lens and anterior pituitary placode. Development. 2005;132:1579-90 pubmed
    ..During mid-somitogenesis, Hedgehog then acts on the established median placode as a necessary and sufficient signal to specify pituitary cell types. ..
  5. Endo D, Park M. Molecular characterization of the leopard gecko POMC gene and expressional change in the testis by acclimation to low temperature and with a short photoperiod. Gen Comp Endocrinol. 2004;138:70-7 pubmed
    The gene for proopiomelanocortin (POMC), a common precursor of malanotropins, corticotropin, and beta-endorphin, was isolated and analyzed in the squamata species, the leopard gecko, Eublepharis macularius...
  6. De Marco R, Thiemann T, Groneberg A, Herget U, Ryu S. Optogenetically enhanced pituitary corticotroph cell activity post-stress onset causes rapid organizing effects on behaviour. Nat Commun. 2016;7:12620 pubmed publisher
    ..Altogether, the findings uncover the significance of endocrine pituitary cells for rapidly optimizing behaviour in local antagonistic environments. ..
  7. Song J, Kim H, Gong Z, Liu N, Lin S. Vhnf1 acts downstream of Bmp, Fgf, and RA signals to regulate endocrine beta cell development in zebrafish. Dev Biol. 2007;303:561-75 pubmed
    ..Taken together, our data establish that vhnf1 acts downstream of the signaling pathways of RA, Bmp, and Fgf to regulate pancreas development in zebrafish. ..
  8. Zhang X, Zhong Y, Tian H, Wang W, Ru S. Impairment of the cortisol stress response mediated by the hypothalamus-pituitary-interrenal (HPI) axis in zebrafish (Danio rerio) exposed to monocrotophos pesticide. Comp Biochem Physiol C Toxicol Pharmacol. 2015;176-177:10-6 pubmed publisher
    ..100μg/L MCP pesticide reduced POMC and GR expression in the brain, MC2R and P45011β expression in the head kidney, but enhanced 20β-HSD2 ..
  9. Yokogawa T, Marin W, Faraco J, Pezeron G, Appelbaum L, Zhang J, et al. Characterization of sleep in zebrafish and insomnia in hypocretin receptor mutants. PLoS Biol. 2007;5:e277 pubmed
    ..Our study validates the use of zebrafish for the study of sleep and indicates molecular diversity in sleep regulatory networks across vertebrates. ..
  10. Liang Y, Huang G, Ying G, Liu S, Jiang Y, Liu S, et al. A time-course transcriptional kinetics of the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes in zebrafish eleutheroembryos after exposure to norgestrel. Environ Toxicol Chem. 2015;34:112-9 pubmed publisher
    ..The transcriptional expression levels of Esr1, Ar, Star, Hsd17b3, Fshb, and Pomc were also mediated by 5 ng L(-1) norgestrel or higher during different exposure periods...
  11. Pogoda H, Hammerschmidt M. How to make a teleost adenohypophysis: molecular pathways of pituitary development in zebrafish. Mol Cell Endocrinol. 2009;312:2-13 pubmed publisher
    ..In addition, zebrafish data will be discussed in comparison with current understanding of adenohypophysis development in mouse. ..
  12. Nesan D, Vijayan M. The transcriptomics of glucocorticoid receptor signaling in developing zebrafish. PLoS ONE. 2013;8:e80726 pubmed publisher
    ..Together, this study underscores a critical role for glucocorticoid signaling in programming molecular events essential for zebrafish development. ..
  13. Domen S, Bumaschny V, de Souza F, Franchini L, Nasif S, Low M, et al. Enhancer turnover and conserved regulatory function in vertebrate evolution. Philos Trans R Soc Lond B Biol Sci. 2013;368:20130027 pubmed publisher
    ..We also identify the neuronal regulatory region of zebrafish pomca and confirm that it is not homologous to the mammalian enhancers...
  14. Manoli M, Driever W. nkx2.1 and nkx2.4 genes function partially redundant during development of the zebrafish hypothalamus, preoptic region, and pallidum. Front Neuroanat. 2014;8:145 pubmed publisher
    ..At the neuronal level, nkx2TKD morphants lacked several neurosecretory neuron types, including avp, crh, and pomc expressing cells in the hypothalamus, but still form oxt neurons in the preoptic region...
  15. Wang H, Semenova S, Kuusela S, Panula P, Lehtonen S. Tankyrases regulate glucoregulatory mechanisms and somatic growth via the central melanocortin system in zebrafish larvae. FASEB J. 2015;29:4435-48 pubmed publisher
    ..In the pituitary, TNKS1b is coexpressed with pro-opiomelanocortin a (pomca) gene in corticotropes and melanotropes...
  16. Guner B, Ozacar A, Thomas J, Karlstrom R. Graded hedgehog and fibroblast growth factor signaling independently regulate pituitary cell fates and help establish the pars distalis and pars intermedia of the zebrafish adenohypophysis. Endocrinology. 2008;149:4435-51 pubmed publisher
    ..These data suggest that there are distinct origins and signaling requirements for the PD and PI. ..
  17. Cortés R, Teles M, Oliveira M, Fierro Castro C, Tort L, Cerdá Reverter J. Effects of acute handling stress on short-term central expression of orexigenic/anorexigenic genes in zebrafish. Fish Physiol Biochem. 2018;44:257-272 pubmed publisher
    ..By contrast, the anorexigenic precursors tested, i.e., cart peptides and pomc, exhibited increased expression after acute stress, suggesting their involvement in the anorexigenic effects.
  18. He W, Dai X, Chen X, He J, Yin Z. Zebrafish pituitary gene expression before and after sexual maturation. J Endocrinol. 2014;221:429-40 pubmed publisher
    ..For the first time, we report the quantitative global gene expression patterns at the juvenile and sexual maturity stages. These expression patterns may account for the dynamic neuroendocrine regulation observed in body metabolism. ..
  19. Zheng B, Li S, Liu Y, Li Y, Chen H, Tang H, et al. Spexin Suppress Food Intake in Zebrafish: Evidence from Gene Knockout Study. Sci Rep. 2017;7:14643 pubmed publisher
    ..However, the hyperphagia did not lead to a higher growth rate or body fat percentage. Taken together, our study suggests that SPX1 may serve as a satiety signal molecular by suppressing the AgRP1 in the brain. ..
  20. Eachus H, Bright C, Cunliffe V, Placzek M, Wood J, Watt P. Disrupted-in-Schizophrenia-1 is essential for normal hypothalamic-pituitary-interrenal (HPI) axis function. Hum Mol Genet. 2017;26:1992-2005 pubmed publisher
    ..releasing hormone (crh) neurons, key regulators of the stress axis, develop abnormally, and rx3-derived pomc+?neurons are disorganised...
  21. Facchinello N, Skobo T, Meneghetti G, Colletti E, Dinarello A, Tiso N, et al. nr3c1 null mutant zebrafish are viable and reveal DNA-binding-independent activities of the glucocorticoid receptor. Sci Rep. 2017;7:4371 pubmed publisher
    ..Mutants show higher levels of whole-body cortisol associated with overstimulated basal levels of crh and pomca transcripts along the HPI axis, which is unresponsive to a mechanical stressor...
  22. Pittlik S, Domingues S, Meyer A, Begemann G. Expression of zebrafish aldh1a3 (raldh3) and absence of aldh1a1 in teleosts. Gene Expr Patterns. 2008;8:141-7 pubmed publisher
  23. Dutta S, Dietrich J, Westerfield M, Varga Z. Notch signaling regulates endocrine cell specification in the zebrafish anterior pituitary. Dev Biol. 2008;319:248-57 pubmed publisher
    ..We propose that Notch mediated lateral inhibition regulates the relative numbers of specified hormone cell types in the three pituitary subdomains. ..
  24. de Souza F, Bumaschny V, Low M, Rubinstein M. Subfunctionalization of expression and peptide domains following the ancient duplication of the proopiomelanocortin gene in teleost fishes. Mol Biol Evol. 2005;22:2417-27 pubmed
    The proopiomelanocortin gene (POMC) encodes several bioactive peptides, including adrenocorticotropin hormone, alpha-, beta-, and gamma-melanocyte-stimulating hormone, and the opioid peptide beta-endorphin, which play key roles in ..
  25. Li S, Liu W, Li Z, Li W, Wang Y, Zhou L, et al. greb1 regulates convergent extension movement and pituitary development in zebrafish. Gene. 2017;627:176-187 pubmed publisher
    ..Therefore, our present study indicates that greb1 is a novel regulator for CE movement and pituitary development in zebrafish. ..
  26. Zhao Y, Yang Z, Phelan J, Wheeler D, Lin S, McCabe E. Zebrafish dax1 is required for development of the interrenal organ, the adrenal cortex equivalent. Mol Endocrinol. 2006;20:2630-40 pubmed
    ..Based on these results, we propose that dax1 is the mammalian DAX1 ortholog, functions downstream of ff1b in the regulatory cascades, and is required for normal development and function of the zebrafish interrenal organ...
  27. To T, Hahner S, Nica G, Rohr K, Hammerschmidt M, Winkler C, et al. Pituitary-interrenal interaction in zebrafish interrenal organ development. Mol Endocrinol. 2007;21:472-85 pubmed
    ..In addition, we studied the effects of ACTH receptor (Mc2r) knockdown and dexamethasone (dex) on interrenal development and pituitary feedback...
  28. Griffin A, Parajes S, Weger M, Zaucker A, Taylor A, O Neil D, et al. Ferredoxin 1b (Fdx1b) Is the Essential Mitochondrial Redox Partner for Cortisol Biosynthesis in Zebrafish. Endocrinology. 2016;157:1122-34 pubmed publisher
    ..In summary, by using zebrafish, we generated a ferredoxin knockout model system, which demonstrates for the first time the impact of mitochondrial redox regulation on glucocorticoid biosynthesis in vivo. ..
  29. Quiroz Y, Lopez M, Mavropoulos A, Motte P, Martial J, Hammerschmidt M, et al. The HMG-box transcription factor Sox4b is required for pituitary expression of gata2a and specification of thyrotrope and gonadotrope cells in zebrafish. Mol Endocrinol. 2012;26:1014-27 pubmed publisher
    ..and gsu? expression and reduced levels of gh, whereas other anterior pituitary gland markers including prl, sl?, pomc, and lim3 are not affected. Sox4b is also required for expression of gata2a in the pituitary...
  30. Ziv L, Gothilf Y. Period2 expression pattern and its role in the development of the pineal circadian clock in zebrafish. Chronobiol Int. 2006;23:101-12 pubmed
    ..Thus, a possible role for early photoreception and light-induced zper2 expression in the development of clock-controlled rhythms remains to be investigated. ..
  31. Santos da Rosa J, Alcântara Barcellos H, Fagundes M, Variani C, Rossini M, Kalichak F, et al. Muscarinic receptors mediate the endocrine-disrupting effects of an organophosphorus insecticide in zebrafish. Environ Toxicol. 2017;32:1964-1972 pubmed publisher
    ..by altering the expression of key genes of the neural steroidogenesis, causing downregulation of star, hsp70, and pomc genes...
  32. Muthu V, Eachus H, Ellis P, Brown S, Placzek M. Rx3 and Shh direct anisotropic growth and specification in the zebrafish tuberal/anterior hypothalamus. Development. 2016;143:2651-63 pubmed publisher
    ..ventricular wall, die or are inappropriately specified, the shh(+) anterior recess does not form, and its resident pomc(+), ff1b(+) and otpb(+) Th1(+) cells fail to differentiate...
  33. Ji Y, Buel S, Amack J. Mutations in zebrafish pitx2 model congenital malformations in Axenfeld-Rieger syndrome but do not disrupt left-right placement of visceral organs. Dev Biol. 2016;416:69-81 pubmed publisher
    ..We show Nodal signaling-independent of Pitx2-controls asymmetric expression of the fatty acid elongase elovl6 in zebrafish, pointing to a potential novel pathway during LR organogenesis. ..
  34. Nesan D, Vijayan M. Maternal Cortisol Mediates Hypothalamus-Pituitary-Interrenal Axis Development in Zebrafish. Sci Rep. 2016;6:22582 pubmed publisher
    ..hormonal response corresponded with altered expression of key HPI axis genes, including crf, 11B hydroxylase, pomca, and star, which were upregulated in response to reduced cortisol availability and downregulated when embryos had ..
  35. Pavlidis M, Theodoridi A, Tsalafouta A. Neuroendocrine regulation of the stress response in adult zebrafish, Danio rerio. Prog Neuropsychopharmacol Biol Psychiatry. 2015;60:121-31 pubmed publisher
    ..brain mRNA expression levels of several genes (corticotropin-releasing factor, crf; pro-opiomelanocortin, pomc; glucocorticoid receptor, gr; MR/GR ratio; prolactin, prl; hypocretin/orexin, hcrt; brain-derived neurotrophic ..
  36. Gonzalez Nunez V, Jimenez González A, Barreto Valer K, Rodriguez R. In vivo regulation of the ? opioid receptor: role of the endogenous opioid agents. Mol Med. 2013;19:7-17 pubmed publisher
    ..Knocking down the dre-oprm1 gene significantly modified the mRNA expression of the penk and pomc genes, thus indicating that oprm1 is involved in shaping penk and pomc expression...
  37. Renquist B, Zhang C, Williams S, Cone R. Development of an assay for high-throughput energy expenditure monitoring in the zebrafish. Zebrafish. 2013;10:343-52 pubmed publisher
    ..We show that leptin, insulin, and alpha-melanocyte-stimulating hormone (?-MSH) increase energy expenditure dose dependently in the larval zebrafish...
  38. Liu C, Yu H, Zhang X. Zebrafish embryos/larvae for rapid determination of effects on hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-interrenal (HPI) axis: mRNA expression. Chemosphere. 2013;93:2327-32 pubmed publisher
    ..Furthermore, we studied the effects of PTU or MET on the cross-talk between HPT and HPI axis. The results demonstrated that PTU and MET could affect cross-talk responses in zebrafish embryos/larvae. ..
  39. Devine C, Sbrogna J, Guner B, Osgood M, Shen M, Karlstrom R. A dynamic Gli code interprets Hh signals to regulate induction, patterning, and endocrine cell specification in the zebrafish pituitary. Dev Biol. 2009;326:143-54 pubmed publisher
    ..Given the link between Hh signaling and pituitary adenomas in humans, our data suggest misregulation of Gli function may contribute to these common pituitary tumors. ..
  40. Drew R, Settles M, Churchill E, Williams S, Balli S, Robison B. Brain transcriptome variation among behaviorally distinct strains of zebrafish (Danio rerio). BMC Genomics. 2012;13:323 pubmed publisher
    ..However, this conclusion must be tempered by limitations associated with comparisons among microarray studies and the low level of population-level replication inherent to these studies. ..
  41. Zhang C, Forlano P, Cone R. AgRP and POMC neurons are hypophysiotropic and coordinately regulate multiple endocrine axes in a larval teleost. Cell Metab. 2012;15:256-64 pubmed publisher
    ..This identifies the mechanism by which the central melanocortin system coordinately regulates growth and reproduction in teleosts and suggests it is an important anatomical substrate for evolutionary adaptation. ..
  42. Bergeron S, Tyurina O, Miller E, Bagas A, Karlstrom R. Brother of cdo (umleitung) is cell-autonomously required for Hedgehog-mediated ventral CNS patterning in the zebrafish. Development. 2011;138:75-85 pubmed publisher
    ..This study reveals a role for Boc in ventral CNS cells that receive high levels of Hh and uncovers previously unknown roles for Boc in vertebrate embryogenesis. ..
  43. Cheng X, Chen X, Li D, Jin X, He J, Yin Z. Effects of metronidazole on proopiomelanocortin a gene expression in zebrafish. Gen Comp Endocrinol. 2015;214:87-94 pubmed publisher
    ..In current study, we found that MTZ can induce proopiomelanocortin a (pomca) expression in zebrafish larvae. The effect of MTZ is in stage-sensitive and dose-dependent manner...
  44. Mechaly A, Richardson E, Rinkwitz S. Activity of etv5a and etv5b genes in the hypothalamus of fasted zebrafish is influenced by serotonin. Gen Comp Endocrinol. 2017;246:233-240 pubmed publisher
    ..This is in line with a previously demonstrated anorexigenic function of serotonin. Our results suggest that obesity-associated ETV5 has a food intake stimulating function and that this function is modulated through serotonin. ..
  45. Zhang D, Wang J, Zhou C, Xiao W. Zebrafish akt2 is essential for survival, growth, bone development, and glucose homeostasis. Mech Dev. 2017;143:42-52 pubmed publisher
  46. Liu N, Ren M, Song J, RIOS Y, Wawrowsky K, Ben Shlomo A, et al. In vivo time-lapse imaging delineates the zebrafish pituitary proopiomelanocortin lineage boundary regulated by FGF3 signal. Dev Biol. 2008;319:192-200 pubmed publisher
    ..Pituitary expression of proopiomelanocortin (POMC), the common precursor for adrenocorticotropin (ACTH) of pars distalis corticotropes and alpha-melanocyte-stimulating hormone (alpha-MSH) of pars intermedia ..
  47. Liang Y, Huang G, Ying G, Liu S, Jiang Y, Liu S, et al. The effects of progesterone on transcriptional expression profiles of genes associated with hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes during the early development of zebrafish (Danio rerio). Chemosphere. 2015;128:199-206 pubmed publisher
    ..The overall results from the present study indicate that P4 at environmentally relevant concentrations could cause the potential effects on zebrafish reproductive and adrenal endocrine systems by interfering with the HPG and HPA axes. ..
  48. Wan G, Chan K. A study of somatolactin actions by ectopic expression in transgenic zebrafish larvae. J Mol Endocrinol. 2010;45:301-15 pubmed publisher
  49. Sun L, Xu W, He J, Yin Z. In vivo alternative assessment of the chemicals that interfere with anterior pituitary POMC expression and interrenal steroidogenesis in POMC: EGFP transgenic zebrafish. Toxicol Appl Pharmacol. 2010;248:217-25 pubmed publisher
    Adrenocorticotropin (ACTH) has been considered a classic adrenocorticotropic hormone and the key pituitary-derived peptide controlling steroidogenesis in the adult adrenal...
  50. Cheng X, Chen X, Jin X, He J, Yin Z. Generation and characterization of gsu?:EGFP transgenic zebrafish for evaluating endocrine-disrupting effects. Toxicol Appl Pharmacol. 2014;278:78-84 pubmed publisher
    ..These reporter fish can serve as a novel platform to perform screenings of endocrine-disrupting chemicals (EDCs) in vivo as well. ..
  51. Wolf A, Ryu S. Specification of posterior hypothalamic neurons requires coordinated activities of Fezf2, Otp, Sim1a and Foxb1.2. Development. 2013;140:1762-73 pubmed publisher
  52. Li X, He J, Hu W, Yin Z. The essential role of endogenous ghrelin in growth hormone expression during zebrafish adenohypophysis development. Endocrinology. 2009;150:2767-74 pubmed publisher
    ..Our research here has demonstrated that zebrafish is a unique model for functional studies of endogenous ghrelin, especially during embryonic development. ..
  53. Song Y, Golling G, Thacker T, Cone R. Agouti-related protein (AGRP) is conserved and regulated by metabolic state in the zebrafish, Danio rerio. Endocrine. 2003;22:257-65 pubmed
    Agouti-related protein (AGRP) and proopiomelanocortin (POMC) genes encode secreted hypothalamic factors regulated by metabolic state in mammals and are involved in energy homeostasis...