Hum. Reprod. Advance Access originally published online on June 2, 2009
Human Reproduction 2009 24(9):2303-2309; doi:10.1093/humrep/dep119
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Daily variation of brain-derived neurotrophic factor and cortisol in women with normal menstrual cycles, undergoing oral contraception and in postmenopause
Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics, University of Pisa, Via Roma 35, 56100 Pisa, Italy
1 Correspondence address. Tel: +39-50-503985; Fax: +39-50-553410; E-mail: Nicola.pluchino{at}med.unipi.it
BACKGROUND: Plasma brain-derived neurotrophic factor (BDNF) levels are associated with the hormonal status of women. Moreover, the suprachiasmatic nucleus appears to be implicated in the modulation of BDNF central levels. We aimed to investigate whether BDNF circadian rhythms exist in women and if there is a relationship with cortisol circadian rhythmicity. Moreover, we aimed to establish whether the hormonal status influences BDNF diurnal variations.
METHODS: A total of 30 women were studied: 10 fertile ovulatory women, 10 women undergoing oral contraceptive (OC) therapy and 10 post-menopausal women. Basal BDNF and estradiol levels were assayed in blood samples collected after overnight fasting at regular intervals (08:00, 12:00, 16:00, 20:00, 24:00). BDNF and cortisol levels were measured in samples collected during the follicular and luteal phases in ovulatory women and once a month in OC and post-menopausal women.
RESULTS: Luteal BDNF levels were significantly higher than follicular levels in fertile women (P < 0.001). In OC women, BDNF levels were similar to the follicular BDNF levels, whereas in post-menopausal women, they were significantly lower (P < 0.001). BDNF showed a diurnal rhythm in the follicular phase and in women undergoing OC, although the diurnal rhythm was blunted in the luteal phase. In post-menopausal women, BDNF and cortisol levels significantly decreased during the day.
CONCLUSIONS: BDNF has a diurnal variation in women that is somewhat analogous to cortisol variation; however, the amplitude of the variation in BDNF levels appears to be influenced by ovarian function. Interactions between BDNF, the hypothalamus–pituitary–adrenal axis and sex steroids might play a critical role in the human homeostasis and adaptation.
Key words: BDNF/cortisol/sex hormones/circadian rhythm
Submitted on July 25, 2008; resubmitted on March 31, 2009; accepted on April 7, 2009.