title: Effects of chronic hyperandrogenism and/or administered central nervous system insulin on ovarian manifestation and gonadotropin and steroid secretion.
abstract: OBJECTIVE
  Polycystic ovarian syndrome is characterized by hyperandrogenism and insulin resistance. We studied the effects of central hyperinsulinemia and peripheral hyperandrogenism on gonadotropin secretion, steroid secretion, and ovarian histology in female rats.
  
  
  METHODS
  Experimental in vivo animal study.
  
  
  METHODS
  University research center.
  
  
  METHODS
  250-300 g female Wistar rats.
  
  
  METHODS
  Insertion of testosterone pellets and/or administration of intracerebroventricular (ICV) insulin.
  
  
  METHODS
  Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels before and after GnRH administration; testosterone, insulin, and glucose levels; and ovarian histology.
  
  
  RESULTS
  Compared with control, rats with testosterone implant had a lower LH and higher FSH while rats with testosterone plus insulin had a higher FSH. Intracerebroventricular (ICV) insulin alone increased LH in response to GnRH. Ovarian histology indicated that testosterone-implanted rats had larger ovaries and an increased number of cystic follicles >50 microm as well as substantial theca enlargement. The administration of testosterone did not alter serum insulin, and ICV insulin did not increase testosterone levels.
  
  
  CONCLUSIONS
  We suggest that ICV insulin acts either directly or indirectly to increase the LH responsiveness to GnRH. ICV insulin arrested the maturation of follicles leading to an increase in the number of small follicles. Peripheral androgens stimulated theca enlargement with cystic follicles. The combination of ICV insulin and peripheral androgens attenuated ovarian histologic changes and gonadotropin secretion. Thus, central hyperinsulinemia and peripheral hyperandrogenism may play a role in gonadotropin secretion as well as ovarian morphology.
authors.affiliation: Department of Obstetrics and Gynecology, C. S. Mott Center for Human Growth and Development, Wayne State University-Detroit Medical Center, Hutzel Hospital, 4707 St. Antoine Boulevard, Detroit, MI 48201, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Allon
authors.forename: Richard E
authors.initials: RE
authors.lastname: Leach
authors.forename: Joseph
authors.initials: J
authors.lastname: Dunbar
authors.forename: Michael P
authors.initials: MP
authors.lastname: Diamond
mesh_terms: D000728:Androgens / Q000097:blood / Q000494:pharmacology; D000818:Animals; D002908:Chronic Disease; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D017588:Hyperandrogenism / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006946:Hyperinsulinism / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000097:blood / Q000494:pharmacology
chemical_list: D000728:Androgens; D007004:Hypoglycemic Agents; D007328:Insulin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone