title: Effects of hyperandrogenemia and increased adiposity on reproductive and metabolic parameters in young adult female monkeys.
abstract: Many patients with hyperandrogenemia are overweight or obese, which exacerbates morbidities associated with polycystic ovary syndrome (PCOS). To examine the ability of testosterone (T) to generate PCOS-like symptoms, monkeys received T or cholesterol (control) implants (n = 6/group) beginning prepubertally. As previously reported, T-treated animals had increased neuroendocrine drive to the reproductive axis [increased luteinizing hormone (LH) pulse frequency] at 5 yr, without remarkable changes in ovarian or metabolic features. To examine the combined effects of T and obesity, at 5.5 yr (human equivalent age: 17 yr), monkeys were placed on a high-calorie, high-fat diet typical of Western cultures [Western style diet (WSD)], which increased body fat from <2% (pre-WSD) to 15-19% (14 mo WSD). By 6 mo on WSD, LH pulse frequency in the controls increased to that of T-treated animals, whereas LH pulse amplitude decreased in both groups and remained low. The numbers of antral follicles present during the early follicular phase increased in both groups on the WSD, but maximal follicular size decreased by 50%. During the late follicular phase, T-treated females had greater numbers of small antral follicles than controls. T-treated monkeys also had lower progesterone during the luteal phase of the menstrual cycle. Although fasting insulin did not vary between groups, T-treated animals had decreased insulin sensitivity after 1 yr on WSD. Thus, while WSD consumption alone led to some features characteristic of PCOS, T + WSD caused a more severe phenotype with regard to insulin insensitivity, increased numbers of antral follicles at midcycle, and decreased circulating luteal phase progesterone levels.
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon; wkmcgee@rams.colostate.edu.
authors.forename: W K
authors.initials: WK
authors.lastname: McGee
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon;
authors.forename: C V
authors.initials: CV
authors.lastname: Bishop
authors.affiliation: Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors.forename: C R
authors.initials: CR
authors.lastname: Pohl
authors.affiliation: Department of Reproductive Endocrinology and Infertility, University of California, San Diego, La Jolla, California; and.
authors.forename: R J
authors.initials: RJ
authors.lastname: Chang
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Center for Research in Reproduction, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: J C
authors.initials: JC
authors.lastname: Marshall
authors.affiliation: The Endocrine Technology Support Laboratory, Oregon National Primate Research Center, Beaverton, Oregon;
authors.forename: F K
authors.initials: FK
authors.lastname: Pau
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon; Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon;
authors.forename: R L
authors.initials: RL
authors.lastname: Stouffer
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon; Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors.forename: J L
authors.initials: JL
authors.lastname: Cameron
mesh_terms: D015502:Absorptiometry, Photon; D050154:Adiposity / Q000502:physiology*; D000375:Aging / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002784:Cholesterol / Q000008:administration & dosage / Q000494:pharmacology; D059305:Diet, High-Fat; D004343:Drug Implants; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005951:Glucose Tolerance Test; D007987:Gonadotropin-Releasing Hormone / Q000097:blood; D017588:Hyperandrogenism / Q000150:complications / Q000503:physiopathology*; D007986:Luteinizing Hormone / Q000097:blood; D008253:Macaca mulatta; D008660:Metabolism / Q000502:physiology*; D009043:Motor Activity; D009490:Neurosecretory Systems / Q000502:physiology; D010053:Ovary / Q000033:anatomy & histology / Q000502:physiology; D012098:Reproduction / Q000502:physiology*; D013739:Testosterone / Q000097:blood / Q000172:deficiency / Q000494:pharmacology
chemical_list: D004343:Drug Implants; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D002784:Cholesterol
keywords: amenorrhea; insulin insensitivity; obesity; ovarian follicle; testosterone
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