title: Effects of recombinant activins on steroidogenesis in human granulosa-lutein cells.
abstract: BACKGROUND
  Exerting a broad range of biological effects in various tissues, activins are homo- or heterodimers of activin/inhibin β-subunits (βA, βB, βC, and βE in humans). Although activins A (βAβA), B (βBβB), AB (βAβB), and AC (βAβC) have been demonstrated in the female reproductive system, little is known about their individual functions in the ovary.
  
  
  OBJECTIVE
  To investigate the biological roles and activities of activins in regulating steroidogenesis in human granulosa cells.
  
  
  METHODS
  Human granulosa-lutein cells obtained from 32 patients undergoing in vitro fertilization were used to investigate the effects of activin A, B, AB, and AC on the expression of steroidogenic enzymes and steroid production.
  
  
  METHODS
  An academic research center.
  
  
  METHODS
  mRNA and protein levels were examined by reverse transcription quantitative real-time PCR and Western blot analysis, respectively. The production of estradiol and progesterone was measured by enzyme immunoassay.
  
  
  RESULTS
  P450 aromatase, FSH receptor, and estradiol levels were increased, whereas steroidogenic acute regulatory protein (StAR), LH receptor, and progesterone levels were decreased after treatment with activin A, B, and AB, but not activin AC. FSH or LH induced the production of aromatase/estradiol and StAR/progesterone; however, pretreatment with activin A, B, or AB enhanced the effects of gonadotropins on aromatase/estradiol, but suppressed their effects on StAR/progesterone. Treatment with activin A, B, or AB induced the phosphorylation of SMA- and MAD-related proteins (SMAD2 and 3), whereas activin AC had no such effects. Furthermore, co-culture of activin AC (1-100 ng/mL) with activin A (25 ng/mL) did not alter the effects of activin A on P450 aromatase or StAR mRNA levels.
  
  
  CONCLUSIONS
  Activin A, B, and AB have similar effects on steroidogenesis in human granulosa cells. In contrast, activin AC is not biologically active and does not act as a competitive antagonist.
authors: Department of Obstetrics and Gynecology, Child & Family Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.
authors: Hsun-Ming
authors: HM
authors: Chang
authors: Jung-Chien
authors: JC
authors: Cheng
authors: Christian
authors: C
authors: Klausen
authors: Elizabeth L
authors: EL
authors: Taylor
authors: Peter C K
authors: PC
authors: Leung
mesh_terms: D028341:Activins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D001141:Aromatase / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D006801:Humans; D028322:Inhibin-beta Subunits / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008184:Luteal Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010053:Ovary / Q000166:cytology; D010750:Phosphoproteins / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: C422402:INHBB protein, human; C504186:INHBC protein, human; C504183:INHBE protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C422405:activin A; C103008:inhibin beta A subunit; D000098682:Steroidogenic Acute Regulatory Protein; D028341:Activins; D011374:Progesterone; D004958:Estradiol; D028322:Inhibin-beta Subunits; D001141:Aromatase; C561410:CYP19A1 protein, human