title: Adrenocorticotropic hormone elicits gonadotropin secretion in premenopausal women.
abstract: Does adrenocorticotropic hormone (ACTH) induce gonadotropin release in premenopausal women?
  
  
  
  Administration of ACTH stimulates gonadotropin release, most likely by stimulation of the production of cortisol, in premenopausal women.
  
  
  
  In animal models, acute activation of the hypothalamic-pituitary-adrenal (HPA) axis has been shown to induce gonadotropin release in the presence of sufficiently high estrogen levels. However, it is unknown whether the HPA axis has a similar influence on gonadotropin release in humans.
  
  
  
  This study had a mixed factorial design. A total of 60 healthy female participants participated in the experimental study.
  
  
  
  The study sample comprised three distinct hormonal-based populations according to their levels of progesterone (PROG) and estradiol (E2): (i) low-PROG-low-E2, (ii) low-PROG-high-E2 and (iii) high-PROG-high-E2 women. A low dose (1 µg) of ACTH was administered to all study participants. Serum steroid and gonadotropin concentrations were measured prior to, and at 30 and 90 minutes after, intravenous ACTH administration.
  
  
  
  Mean serum cortisol levels increased significantly following ACTH administration in all groups (P < 0.001). Similarly, the serum levels of 17-OH-PROG, androstenedione, dehydroepiandrosterone and testosterone increased significantly in all groups (P < 0.01). The low-PROG-high-E2 and high-PROG-high-E2 groups exhibited a significant increase in LH and FSH levels (P < 0.001), whereas the low-PROG-low-E2 group demonstrated blunted LH and FSH responses to ACTH administration (P < 0.05).
  
  
  
  Testing was performed during the luteal phase of the natural menstrual cycle. Testing during the follicular phase might have elicited premature, or more pronounced, LH surges in response to ACTH administration.
  
  
  
  Our findings suggest a novel mechanism by which the adrenal cortex functions as a mediator of gonadotropin release. These findings contribute to a greater understanding of the influence of acute stress on reproductive endocrinology.
  
  
  
  Funding was received from the Erasmus University Medical Center. The authors have no conflicts of interest.
  
  
  
  EudraCT Number 2012-005640-14.
authors: Department of Psychiatry, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors: Jurate
authors: J
authors: Aleknaviciute
authors: Department of Psychiatry, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors: Joke H M
authors: JH
authors: Tulen
authors: Department of Psychiatry, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors: Mirjam
authors: M
authors: Timmermans
authors: Department of Clinical Chemistry, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors: Yolanda B
authors: YB
authors: de Rijke
authors: Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors: Elisabeth F C
authors: EF
authors: van Rossum
authors: Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors: Frank H
authors: FH
authors: de Jong
authors: Department of Psychiatry, Erasmus MC, University Medical Center, Rotterdam, the Netherlands s.kushner@erasmusmc.nl.
authors: Steven A
authors: SA
authors: Kushner
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000328:Adult; D000735:Androstenedione / Q000097:blood*; D003687:Dehydroepiandrosterone / Q000097:blood; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood*; D064368:Healthy Volunteers; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000097:blood*; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D013739:Testosterone / Q000097:blood; D055815:Young Adult
chemical_list: D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D011374:Progesterone; D004958:Estradiol; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D006854:Hydrocortisone
keywords: adrenal steroids; gonadotropin release; hormonal contraceptives; low-dose ACTH test