Timing of Initiation of the Preovulatory Luteinizing Hormone Surge and Its Relationship with the Circadian Cortisol Rhythm in the Human

Abstract

The relationship between the hypothalamo-pituitary-gonadal (HPG) axis and the hypothalamo-pituitary-adrenal (HPA) axis has been well documented in the rat. In most cases, a negative coupling was observed and an inhibitory effect of the HPA axis upon the HPG was shown. In the female rat, a marked circadian rhythm of corticosterone plasma values is observed during each day of the estrous cycle, with maximal values around 08:00 p.m. The preovulatory luteinizing hormone (LH) surge also occurs at 08:00 p.m. on the day of proestrus. Here we measured circadian variations of plasma cortisol in humans in relation with the time of initiation of the preovulatory LH surge. Blood samples were taken at 08:00 a.m., 12:00 a.m., 04:00 p.m., 08:00 p.m., 12:00 p.m., and 04:00 a.m. from 19 subjects for 4 consecutive days, once 17β-estradiol (E₂) values reached 125 pg/ml (days 7–10 of the menstrual cycle). Serum E₂ and LH determinations were performed by microparticle enzyme immunoassays. Serum progesterone and plasma cortisol determinations were made using RIA methods. For plasma cortisol values, a marked circadian rhythm, with 2- to 3-fold higher values during the morning than during the afternoon, was almost identical before, during and after the LH surge. However, values were generally higher during the follicular phase than during the luteal phase. Maximum cortisol values occurred between 04:00 and 08:00 a.m. and minimal cortisol values between 04:00 and 08:00 p.m. Initiation of the LH surge (50% over the mean of previous values) occurred at 04:00 a.m. (20% of the cases) or at 08:00 a.m. (80% of the cases). There was a strong coupling between the onset of the surge and the acrophase of the cortisol circadian rhythm: maximal cortisol plasma values were seen at 04:00 a.m. when the LH preovulatory surge started at 04:00 a.m. and 08:00 a.m. when it started at 08:00 a.m. The present results show that the positive coupling documented in the female rat between the HPA and the HPG axis at the time of preovulatory LH surge is also present during the menstrual cycle in the human.

Sleep, Circadian Rhythms, and Fertility

“…In addition to the infradian (>24 h) ovulatory cycle every 28 days, women display 24-h rhythmicity of the preovulatory LH surge that typically occurs in the early morning hours [23,53,54].…”

Estradiol Induces Diurnal Shifts in GABA Transmission to Gonadotropin-Releasing Hormone Neurons to Provide a Neural Signal for Ovulation

“…In rodents, estradiol interacts with a circadian signal so that the surge is timed to a specific time of day, specifically late afternoon in nocturnal species (Norman et al, 1973;Legan and Karsch, 1975;Christian et al, 2005). In many women, the diurnal tendency persists as the LH surge tends to occur in the early morning (Kerdelhue et al, 2002).…”

hormone nuclear receptor (EcR) exhibits circadian cycling in certain tissues, but not others, during development in Rhodnius prolixus (Hemiptera)

“…Circulating levels of these hormones show daily rhythms in many vertebrates, e.g. oestradiol (Hau et al 2001;Bao et al 2003), corticosteroids (Kerdelhue et al 2002;Wright et al 2003), testosterone (Schulz et al 1995;Hau et al 2001) and thyroxine (Leiner and MacKenzie 2001). The expression and/or density of several of these nuclear hormone receptors has been shown to cycle with a daily rhythm in a small but growing number of reports and is presumed to reflect the rhythmic induction of the receptor by hormones, e.g.…”