Skip to main content
SpringerLink
Log in

Regulation of Steroid Hormone Biosynthesis by the Cytoskeleton

  • Original Article
  • Published:
Lipids

Abstract

Steroid hormones are synthesized in response to signaling cascades initiated by the trophic peptide hormones derived from the anterior pituitary. The mechanisms by which these peptide hormones regulate steroid hormone production are multifaceted and include controlling the transcription of steroidogenic genes, regulating cholesterol (substrate) uptake and transport, modulating steroidogenic enzyme activity, and controlling electron availability. Cytoskeletal polymers such as microfilaments and microtubules have also been implicated in regulating steroidogenesis. Of note, steroidogenesis is a multi-step process that occurs in two organelles, the endoplasmic reticulum (ER) and the mitochondrion. However, the precise mechanism by which substrates are delivered back and forth between these two organelles is unknown. In this review we will discuss the role of components of the cytoskeleton in conferring optimal steroidogenic potential. Finally, we present data that identifying a novel mechanism by which sphingosine-1-phosphate induces mitochondrial trafficking to promote steroidogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

ACTH:

Adrenocorticotropin

ER:

Endoplasmic reticulum

LDL:

Low density lipoprotein

LDLR:

Low density lipoprotein receptor

SR-BI:

Scavenger receptor type BI

HDL:

High density lipoprotein

CARS:

Coherent anti-Stokes Raman scattering

PKA:

Protein kinase A

NPC1:

Niemann-Pick type C1

HSL:

Hormone sensitive lipase

3βHSD:

3 Beta hydroxysteroid dehydrogenase

P450scc:

P450 side chain cleavage

DHEA:

Dehydroepiandrosterone

S1P:

Sphingosine-1-phosphate

References

  1. Sewer MB, Dammer EB, Jagarlapudi S (2007) Transcriptional regulation of adrenocortical steroidogenic gene expression. Drug Metab Rev 39:371–388

    Article  PubMed  CAS  Google Scholar 

  2. Sewer MB, Waterman MR (2003) ACTH modulation of transcription factors responsible for steroid hydroxylase gene expression in the adrenal cortex. Microsc Res Tech 61:300–307

    Article  PubMed  CAS  Google Scholar 

  3. Yasumura Y, Buonassisi V, Sato G (1966) Clonal analysis of differentiated function in animal cell cultures. I. Possible correlated maintenance of differentiated function and the diploid karyotype. Cancer Res 26:529–535

    PubMed  CAS  Google Scholar 

  4. Yasumura Y (1968) Retention of differentiated function in clonal animal cell lines, particularly hormone-secreting cultures. Am Zool 8:285–305

    PubMed  CAS  Google Scholar 

  5. Cuprak LJ, Lammi CJ, Bayer RC (1977) Scanning electron microscopy of induced cell rounding of mouse adrenal cortex tumor cells in culture. Tissue Cell 9:667–680

    Article  PubMed  CAS  Google Scholar 

  6. Mattson P, Kowal J (1978) The ultrastructure of functional mouse adrenal cortical tumor cells in vitro. Differentiation 11:75–88

    Article  PubMed  CAS  Google Scholar 

  7. Voorhees H, Aschenbrenner J, Carnes J, Mrotek J (1984) Rounding and steroidogenesis of enzyme- and ACTH-treated Y-1 mouse adrenal tumor cells. Cell Biol Int Rep 8:483–497

    Article  PubMed  CAS  Google Scholar 

  8. Han JD, Rubin CS (1996) Regulation of cytoskeleton organization and paxillin dephosphorylation by cAMP. J Biol Chem 271:29211–29215

    Article  PubMed  CAS  Google Scholar 

  9. Whitehouse BJ, Gyles SL, Squires PE, Sayed SB, Burns CJ, Persaud SJ, Jones PM (2002) Interdependence of steroidogenesis and shape changes in Y1 adrenocortical cells: studies with inhibitors of phosphoprotein phosphatases. J Endocrinol 172:583–593

    Article  PubMed  CAS  Google Scholar 

  10. Connelly MA, Williams DL (2004) SR-BI and HDL cholesteryl ester metabolism. Endocr Res 30:697–703

    Article  PubMed  CAS  Google Scholar 

  11. Azhar S, Leers-Sucheta S, Reaven E (2003) Cholesterol uptake in adrenal and gonadal tissues: the SR-BI and “selective” pathway connection. Front Biosci 8:998–1029

    Article  Google Scholar 

  12. Crivello JF, Jefcoate CR (1978) Mechanisms of corticotropin action in rat adrenal cells. I. The effects of inhibitors of protein synthesis and of microfilament formation on corticosterone synthesis. Biochem Biophys Res Commun 542:315–329

    CAS  Google Scholar 

  13. Rajan VP, Menon KM (1985) Involvement of microtubules in lipoprotein degradation and utilization for steroidogenesis in cultured rat luteal cells. Endocrinology 117:2408–2416

    Article  PubMed  CAS  Google Scholar 

  14. Cortese F, Wolff J (1978) Cytochalasin-stimulated steroidogenesis from high density lipoproteins. J Cell Biol 77:507–516

    Article  PubMed  CAS  Google Scholar 

  15. Osawa S, Betz G, Hall PF (1984) Role of actin in the responses of adrenal cells to ACTH and cyclic AMP: inhibition by DNase I. J Cell Biol 99:1335–1342

    Article  PubMed  CAS  Google Scholar 

  16. Nan X, Potma EO, Xie XS (2006) Nonperturbative chemical imaging of organelle transport in living cells with coherent anti-strokes Raman scattering microscopy. Biophysical J 91:728–735

    Article  CAS  Google Scholar 

  17. Lee LJ, Chen JS, Ko TL, Wang SM (2001) Mechanism of colchicine-induced steroidogenesis in rat adrenocortical cells. J Cell Biochem 81:162–171

    Article  PubMed  CAS  Google Scholar 

  18. Sackett DL, Wolff J (1986) Cyclic AMP-independent stimulation of steroidogenesis in Y-1 adrenal tumor cells by antimitotic agents. Biochim Biophys Acta 888:163–170

    Article  PubMed  CAS  Google Scholar 

  19. Shiver TM, Sackett DL, Knipling L, Wolff J (1992) Intermediate filaments and steroidogenesis in adrenal Y-1 cells: acrylamide stimulation of steroid production. Endocrinology 131:201–207

    Article  PubMed  CAS  Google Scholar 

  20. Strauss JF 3rd, Liu P, Christenson LK, Watari H (2002) Sterols and intracellular vesicular trafficking: lessons from the study of NPC1. Steroids 67:947–951

    Article  PubMed  CAS  Google Scholar 

  21. Zhang M, Liu P, Dwyer NK, Christenson LK, Fujimoto T, Martinez F, Comly M, Hanover JA, Blanchette-Mackie EJ, Strauss JF 3rd (2002) MLN64 mediates mobilization of lysosomal cholesterol to steroidogenic mitochondria. J Biol Chem 277:33300–33310

    Article  PubMed  CAS  Google Scholar 

  22. Kraemer FB, Shen WJ (2002) Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis. J Lipid Res 43:1585–1594

    Article  PubMed  CAS  Google Scholar 

  23. Brasaemle DL, Levin DM, Adler-Wailes DC, Londos C (2000) The lipolytic stimulation of 3T3-L1 adipocytes promotes the translocation of hormone-sensitive lipase to the surfaces of lipid storage droplets. Biochim Biophys Acta 1483(2):251–262

    Google Scholar 

  24. Denkova R, Ivanov I, Dimitrova M (1992) Microtubules and regulation of granulosa cell steroidogenesis by porcine granulosa cell conditioned medium. Endocr Regul 26:195–199

    PubMed  CAS  Google Scholar 

  25. Carnegie JA, Tsang BK (1987) Microtubules and the calcium-dependent regulation of rat granulosa cell steroidogenesis. Biol Reprod 36:1007–1015

    Article  PubMed  CAS  Google Scholar 

  26. Carnegie JA, Dardick I, Tsang BK (1987) Microtubules and the gonadotropic regulation of granulosa cell steroidogenesis. Endocrinology 120:819–828

    PubMed  CAS  Google Scholar 

  27. Benis R, Mattson P (1989) Microtubules, organelle transport, and steroidogenesis in cultured adrenocortical tumor cells. 1. An ultrastructural analysis of cells in which basal and ACTH-induced steroidogenesis was inhibited by taxol. Tissue Cell 21:479–494

    Article  PubMed  CAS  Google Scholar 

  28. Benis R, Mattson P (1989) Microtubules, organelle transport, and steroidogenesis in cultured adrenocortical tumor cells. 2. Reversibility of taxol’s inhibition of basal and ACTH-induced steroidogenesis is unaccompanied by reversibility of taxol-induced changes in cell ultrastructure. Tissue Cell 21:687–698

    Article  PubMed  CAS  Google Scholar 

  29. Murdoch WJ (1996) Microtubular dynamics in granulosa cells of periovulatory follicles and granulosa-derived (large) lutein cells of sheep: relationships to the steroidogenic folliculo-luteal shift and functional luteolysis. Biol Reprod 54:1135–1140

    Article  PubMed  CAS  Google Scholar 

  30. Gregoraszczuk EL, Stlomczynska M (1996) The cytoskeleton proteins and LH-regulated steroidogenesis of porcine luteal cells. Folia Histochem Cytobiol 34:35–39

    PubMed  CAS  Google Scholar 

  31. Chen TT, Massey PJ, Caudle MR (1994) The inhibitory action of taxol on granulosa cell steroidogenesis is reversible. Endocrinology 134:2178–2183

    Article  PubMed  CAS  Google Scholar 

  32. Feuilloley M, Contesse V, Lefebvre H, Delarue C, Vaudry H (1994) Effects of selective disruption of cytoskeletal elements on steroid secretion by human adrenocortical slices. Am J Physiol 266:E202–E210

    PubMed  CAS  Google Scholar 

  33. De Loof A, Vanden J, Janssen I (1996) Hormones and the cytoskeleton of animals and plants. Int Rev Cytol 166:1–58

    Article  PubMed  Google Scholar 

  34. Hall PF, Almahbobi G (1997) Roles of microfilaments and intermediate filaments in adrenal steroidogenesis. Microsc Res Tech 36:463–479

    Article  PubMed  CAS  Google Scholar 

  35. Morris RL, Hollenbeck PJ (1995) Axonal transport of mitochondria along microtubules and F-actin in living vertebrate neurons. J Cell Biol 131:1315–1326

    Article  PubMed  CAS  Google Scholar 

  36. Morris RL, Hollenbeck PJ (1993) The regulation of bidirectional mitochondrial transport is coordinated with axonal outgrowth. J Cell Sci 104:917–927

    PubMed  Google Scholar 

  37. Davis AF, Clayton DA (1996) In situ localization of mitochondrial DNA replication in intact mammalian cells. J Cell Biol 135:883–893

    Article  PubMed  CAS  Google Scholar 

  38. Chada SR, Hollenbeck PJ (2004) Nerve growth factor signaling regulates motility and docking of axonal mitochondria. Curr Biol 14:1272–1276

    Article  PubMed  CAS  Google Scholar 

  39. Ball EH, Singer SJ (1982) Mitochondria are associated with microtubules and not with intermediate filaments in cultured fibroblasts. Proc Natl Acad Sci 79:123–126

    Article  PubMed  CAS  Google Scholar 

  40. Yi M, Weaver D, Hajnoczky G (2004) Control of mitochondrial motility and distribution by the calcium signal: a homeostatic circuit. J Cell Biol 167:661–672

    Article  PubMed  CAS  Google Scholar 

  41. Summerhayes IC, Wong D, Chen LB (1983) Effect of microtubules and intermediate filaments on mitochondrial distribution. J Cell Sci 61:87–105

    PubMed  CAS  Google Scholar 

  42. Stromer MH, Bendayan M (1990) Immunocytochemical identification of cytoskeletal linkages to smooth muscle cell nuclei and mitochondria. Cell Motil Cytoskeleton 17:11–18

    Article  PubMed  CAS  Google Scholar 

  43. Tanaka Y, Kanai Y, Okada Y, Nonaka S, Takeda S, Harada A, Hirokawa N (1998) Targeted disruption of mouse conventional kinesin heavy chain, kif5B, results in abnormal perinuclear clustering of mitochondria. Cell 93:1147–1158

    Article  PubMed  CAS  Google Scholar 

  44. Miki H, Okada Y, Hirokawa N (2005) Analysis of the kinesin superfamily: insights into the structure and function. Trends Cell Biol 15:467–476

    Article  PubMed  CAS  Google Scholar 

  45. Kwok BH, Kapoor TM (2007) Microtubule flux: drivers wanted. Curr Opin Cell Biol 19:36–42

    Article  PubMed  CAS  Google Scholar 

  46. Hollenbeck PJ, Saxton WM (2005) The axonal transport of mitochondria. J Cell Sci 118:5411–5419

    Article  PubMed  CAS  Google Scholar 

  47. Gross SP (2004) Hither and yon: a review of bi-directional microtubule-based transport. Phys Biol 1:R1–R11

    Article  PubMed  CAS  Google Scholar 

  48. Ozbay T, Rowan A, Leon A, Patel P, Sewer MB (2006) Cyclic adenosine 5′-monophosphate-dependent sphingosine-1-phosphate biosynthesis induces human CYP17 gene transcription by activating cleavage of sterol regulatory element binding protein 1. Endocrinology 147:1427–1437

    Article  PubMed  CAS  Google Scholar 

  49. Rabano M, Pena A, Brizuela L, Marino A, Macarulla JM, Trueba M, Gomez-Munoz A (2003) Sphingosine-1-phosphate stimulates cortisol secretion. FEBS Lett 535:101–105

    Article  PubMed  CAS  Google Scholar 

  50. Cai Z, Kwintkiewicz J, Young M, Stocco D (2007) Prostaglandin E2 increases CYP19 expression in rat granulosa cells: implication of GATA-4. Mol Cell Endocrinol 263:181–189

    Article  PubMed  CAS  Google Scholar 

  51. Brizuela L, Rabano M, Pena A, Gangoiti P, Macarulla JM, Trueba M, Gomez-Munoz A (2006) Sphingosine-1-phosphate: a novel stimulator of aldosterone secretion. J Lipid Res 47:1238–1249

    Article  PubMed  CAS  Google Scholar 

  52. Brizuela L, Rabano M, Gangoiti P, Narbona N, Macarulla JM, Trueba M, Gomez-Munoz A (2007) Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3 K/PKB and MEK/ERK1/2 pathways. J Lipid Res 48:2264–2274

    Google Scholar 

  53. Goparaju SK, Jolly PS, Watterson KR, Bektas M, Alvarez S, Sarkar S, Mel L, Ishii I, Chun J, Milstien S, Spiegel S (2005) The S1P2 receptor negatively regulates platelet-derived growth factor-induced motility and proliferation. Mol Cell Biol 25:4237–4249

    Article  PubMed  CAS  Google Scholar 

  54. Spiegel S, Milstien S (2003) Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat Rev Mol Cell Biol 4:397–407

    Article  PubMed  CAS  Google Scholar 

  55. Sarkar S, Maceyka M, Hait NC, Paugh SW, Sankala H, Milstien S, Spiegel S (2005) Sphingosine kinase 1 is required for migration, proliferation and survival of MCF-7 human breast cancer cells. FEBS Lett 579:5313–5317

    Article  PubMed  CAS  Google Scholar 

  56. Hait NC, Sarkar S, Le Stunff H, Mikami A, Maceyka M, Milstien S, Spiegel S (2005) Role of sphingosine kinase 2 in cell migration toward epidermal growth factor. J Biol Chem 280:29462–29469

    Article  PubMed  CAS  Google Scholar 

  57. Rosenfeldt HM, Hobson JP, Maceyka M, Olivera A, Nava VE, Milstien S, Spiegel S (2001) EDG-1 links the PDGF receptor to Src and focal adhesion kinase activation leading to lamellipodia formation and cell migration. FASEB J 15:2649–2659

    Article  PubMed  CAS  Google Scholar 

  58. Le Stunff H, Mikami A, Giussani P, Hobson JP, Jolly PS, Milstien S, Spiegel S (2004) Role of sphingosine-1-phosphate in epidermal growth factor-induced chemotaxis. J Biol Chem 279:34290–34297

    Article  PubMed  CAS  Google Scholar 

  59. Jolly PS, Bektas M, Olivera A, Gonzalez-Espinosa C, Proia RL, Rivera J, Milstien S, Spiegel S (2004) Transactivation of sphingosine-1-phosphate receptors by FcepsilonRI triggering is required for normal mast cell degranulation and chemotaxis. J Exp Med 199:959–970

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work is supported by the National Institutes of Health/National Institute of General Medical Sciences (GM073241) and by a CAREER award from the National Science Foundation (MCB0347682).

Author information

Authors and Affiliations

  1. School of Biology and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, 30332-0230, USA

    Marion B. Sewer & Donghui Li

Authors
  1. Marion B. Sewer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Donghui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marion B. Sewer.

About this article

Cite this article

Sewer, M.B., Li, D. Regulation of Steroid Hormone Biosynthesis by the Cytoskeleton. Lipids 43, 1109–1115 (2008). https://doi.org/10.1007/s11745-008-3221-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-008-3221-2

Keywords

Search

Navigation