STUDY QUESTION Does adrenocorticotropic hormone (ACTH) induce gonadotropin release in premenopausal women? SUMMARY ANSWER Administration of ACTH stimulates gonadotropin release, most likely by stimulation of the production of cortisol, in premenopausal women. WHAT IS KNOWN ALREADY 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. STUDY DESIGN, SIZE, DURATION This study had a mixed factorial design. A total of 60 healthy female participants participated in the experimental study. PARTICIPANTS/MATERIALS, SETTING, METHODS 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. MAIN RESULTS AND THE ROLE OF CHANCE 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). LIMITATIONS, REASONS FOR CAUTION 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. WIDER IMPLICATIONS OF THE FINDINGS 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. STUDY FUNDING/COMPETING INTEREST(S) Funding was received from the Erasmus University Medical Center. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER EudraCT Number 2012-005640-14.

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Human Reproduction
Department of Psychiatry

Aleknavičiūtė, J., Tulen, J., Timmermans, M. (Mirjam), de Rijke, Y., van Rossum, L., de Jong, F., & Kushner, S. (2016). Adrenocorticotropic hormone elicits gonadotropin secretion in premenopausal women. Human Reproduction, 31(10), 2360–2368. doi:10.1093/humrep/dew190