Regulation of a putative corticosteroid, 17,21-dihydroxypregn-4-ene,3,20-one, in sea lamprey, Petromyzon marinus

Gen Comp Endocrinol. 2014 Jan 15;196:17-25. doi: 10.1016/j.ygcen.2013.11.008. Epub 2013 Nov 25.


In higher vertebrates, in response to stress, the hypothalamus produces corticotropin-releasing hormone (CRH), which stimulates cells in the anterior pituitary to produce adrenocorticotropic hormone (ACTH), which in turn stimulates production of either cortisol (F) or corticosterone (B) by the adrenal tissues. In lampreys, however, neither of these steroids is present. Instead, it has been proposed that the stress steroid is actually 17,21-dihydroxypregn-4-ene-3,20-dione (11-deoxycortisol; S). However, there have been no studies yet to determine its mechanism of regulation or site of production. Here we demonstrate that (1) intraperitoneal injections of lamprey-CRH increase plasma S in a dose dependent manner, (2) intraperitoneal injections of four lamprey-specific ACTH peptides at 100μg/kg, did not induce changes in plasma S concentrations in either males or females; (3) two lamprey-specific gonadotropin-releasing hormones (GnRH I and III) and arginine-vasotocin (AVT), all at single doses, stimulated S production as well as, or to an even greater extent than CRH; (4) sea lamprey mesonephric kidneys, in vitro, converted tritiated 17α-hydroxyprogesterone (17α-P) into a steroid that had the same chromatographic properties (on HPLC and TLC) as S; (5) kidney tissues released significantly more immunoassayable S into the incubation medium than gill, liver or gonad tissues. One interpretation of these results is that the corticosteroid production of the sea lamprey, one of the oldest extant vertebrates, is regulated through multiple pathways rather than the classical HPI-axis. However, the responsiveness of this steroid to the GnRH peptides means that a reproductive rather than a stress role for this steroid cannot yet be ruled out.

Keywords: 17,21-Dihydroxypregn-4-ene-3,20-dione; Adrenocorticotropic hormone; Corticotropin releasing hormone; Lamprey; Steroid hormone; Stress axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / pharmacology
  • Amino Acid Sequence
  • Animals
  • Anti-Inflammatory Agents / blood
  • Chromatography, Thin Layer
  • Corticosterone / blood*
  • Corticotropin-Releasing Hormone / chemistry
  • Corticotropin-Releasing Hormone / pharmacology*
  • Cortodoxone / blood*
  • Dose-Response Relationship, Drug
  • Female
  • Gonadotropin-Releasing Hormone / pharmacology*
  • Hormones / pharmacology*
  • Hypothalamo-Hypophyseal System / drug effects*
  • Hypothalamo-Hypophyseal System / metabolism
  • Injections, Intraperitoneal
  • Lampreys / metabolism*
  • Male
  • Molecular Sequence Data
  • Radioimmunoassay
  • Sequence Homology, Amino Acid
  • Vasotocin / pharmacology*


  • Anti-Inflammatory Agents
  • Hormones
  • Gonadotropin-Releasing Hormone
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Vasotocin
  • Corticosterone
  • Cortodoxone