title: Rapid impact of progesterone on the neuronal growth cone.
abstract: In the last two decades, sensory neurons and Schwann cells in the dorsal root ganglia (DRG) were shown to express the rate-limiting enzyme of the steroid synthesis, cytochrome P450 side-chain cleavage enzyme (P450scc), as well as the key enzyme of progesterone synthesis, 3β-hydroxysteroid dehydrogenase (3β-HSD). Thus, it was well justified to consider that DRG neurons similarly are able to synthesize progesterone de novo from cholesterol. Because direct progesterone effects on axonal outgrowth in peripheral neurons have not been investigated up to now, the present study provides the first insights into the impact of exogenous progesterone on axonal outgrowth in DRG neurons. Our studies including microinjection and laser scanning microscopy demonstrate morphological changes especially in the neuronal growth cones after progesterone treatment. Furthermore, we were able to detect a distinctly enhanced motility only a few minutes after the start of progesterone treatment using time-lapse imaging. Investigation of the cytoskeletal distribution in the neuronal growth cone before, during, and after progesterone incubation revealed a rapid reorganization of actin filaments. To get a closer idea of the underlying receptor mechanisms, we further studied the expression of progesterone receptors in DRG neurons using RT-PCR and immunohistochemistry. Thus, we could demonstrate for the first time that classical progesterone receptor (PR) A and B and the recently described progesterone receptor membrane component 1 (PGRMC1) are expressed in DRG neurons. Antagonism of the classical progesterone receptors by mifepristone revealed that the observed progesterone effects are transmitted through PR-A and PR-B.
authors.affiliation: Faculty of Medicine, Institute of Anatomy and Molecular Embryology, Ruhr-University Bochum, 44780 Bochum, Germany. carsten.theiss@rub.de.
authors.forename: Laura
authors.initials: L
authors.lastname: Olbrich
authors.forename: Lisa
authors.initials: L
authors.lastname: Wessel
authors.forename: Ajeesh
authors.initials: A
authors.lastname: Balakrishnan-Renuka
authors.forename: Marion
authors.initials: M
authors.lastname: Böing
authors.forename: Beate
authors.initials: B
authors.lastname: Brand-Saberi
authors.forename: Carsten
authors.initials: C
authors.lastname: Theiss
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects; D000818:Animals; D030161:Avian Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006727:Hormone Antagonists / Q000494:pharmacology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D011374:Progesterone / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D059008:Time-Lapse Imaging; D000097573:Red Fluorescent Protein
chemical_list: D030161:Avian Proteins; D049452:Green Fluorescent Proteins; D006727:Hormone Antagonists; D008164:Luminescent Proteins; D008565:Membrane Proteins; D016900:Neurofilament Proteins; D011374:Progesterone; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D011993:Recombinant Fusion Proteins; D000097573:Red Fluorescent Protein; C101118:progesterone receptor A; C097314:progesterone receptor B; C061195:neurofilament protein M