Evidence for hypothalamic control of the diurnal rhythms in prolactin and melatonin in the fetal sheep during late gestation.

Abstract

We have investigated the effect of surgical disconnection of the fetal hypothalamus and pituitary (HPD) on generation of the daily rhythm in fetal plasma melatonin and PRL concentrations under long and short photoperiods. Fetal HPD or a sham operation was carried out at around 110 days gestation. Ewes carrying either HPD fetal sheep (n = 10) or intact fetal sheep (n = 12) were exposed to a long light (LL; 16 h of light and 8 h of darkness) or a short light (SL; 8 h of light and 16 h of darkness) regimen for the remainder of gestation. All ewes were subjected to a 24-h blood-sampling experiment (13 samples collected between 0900-0900 h the following day) between 135-140 days gestation, and fetal and maternal plasma melatonin and PRL concentrations were measured using specific RIAs. The hormonal data were analyzed using multifactorial analysis of variance and cosinor analysis. There was an increase in maternal melatonin concentrations during the dark phase in each lighting regimen in ewes carrying HPD or intact fetal sheep. In the SL regimen, there was also a significant increase in fetal melatonin concentrations during the dark phase in the HPD and intact groups. Under LL conditions, however, fetal melatonin concentrations were only consistently increased during the dark phase in the intact, not the HPD, group. The 24-h mean fetal plasma concentrations of PRL were significantly higher (P < 0.001) in both intact and HPD fetuses in the LL (intact, 111.0 +/- 22.0 pg/ml; HPD, 37.6 +/- 7.3 pg/ml) than in the SL regimen (intact, 37.8 +/- 18.4 pg/ml; HPD, 6.7 +/- 4.3 pg/ml). There was also a significant interaction (P < 0.001) between the effects of fetal surgical treatment and time of day on fetal PRL concentrations. In the intact group, fetal PRL concentrations were significantly higher (P < 0.05) at 1300 and 1700 h than between 0300-0700 h in both lighting conditions. Cosinor analysis also identified a significant rhythm in 8 of the 12 fetal PRL profiles in the intact group. In contrast, in the HPD group, there was no significant effect of time of day on fetal PRL in either the LL or SL regimen, and cosinor analysis only identified a significant rhythm in 2 of the 10 fetal PRL profiles in this group. We have, therefore, demonstrated that in the fetal sheep, HPD resulted in abolition of the diurnal melatonin rhythm under LL conditions and in the loss of the diurnal PRL rhythm under LL and SL conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Melatonin improves placental efficiency and birth weight and increases the placental expression of antioxidant enzymes in undernourished pregnancy

“…Our data show that basal plasma melatonin concentrations were higher in the maternal than the fetal compartment, confirming other studies reporting in different species that melatonin crosses the placenta, and that fetal circulating melatonin is of maternal origin [39–42]. The concentrations measured in maternal plasma following melatonin treatment were similar to those found in other studies using pregnant rats [39, 43].…”

“…In support of this line of thinking, data in this study show that maternal treatment with melatonin in undernourished pregnancy improved placental efficiency and restored birth weight to control levels. Our data show that basal plasma melatonin concentrations were higher in the maternal than the fetal compartment, confirming other studies reporting in different species that melatonin crosses the placenta, and that fetal circulating melatonin is of maternal origin [39][40][41][42]. The concentrations measured in maternal plasma following melatonin treatment were similar to those found in other studies using pregnant rats [39,43].…”

Evidence of a role for melatonin in fetal sheep physiology: direct actions of melatonin on fetal cerebral artery, brown adipose tissue and adrenal gland

“…Melatonin receptors have been identified in several fetal tissues of a variety of species (Williams et al 1991, 1997; Rivkees & Reppert, 1991; Helliwell & Williams, 1994; Drew et al 1998; Thomas et al 2002; Jimenez‐Jorge et al 2005); with exception made of the capuchin fetal adrenal gland (Torres‐Farfan et al 2004; Torres‐Farfan et al 2006 b ), direct melatonin actions in fetal tissues have not been assessed to date. In the fetal sheep, circulating melatonin concentration ranges from about 0.15 n m in the day time to 0.30 n m at night time (Yellon & Longo, 1988; McMillen & Nowak, 1989; Houghton et al 1995). In the present study, melatonin concentrations in the nanomolar range or lower have direct inhibitory effects: (a) in the middle fetal sheep cerebral arteries and the fetal sheep brown adipose tissue response to noradrenaline and (b) in the fetal sheep adrenal gland response to ACTH.…”

Melatonin Modulation of the Daily Prolactin Secretion in Intact and Ovariectomized Ewes

“…By autumn, an evening peak of prolactin is also noted until its complete disappearance in winter under short-day conditions [11, 13]. Changes in the 24-hour prolactin rhythm have been demonstrated also in fetal sheep [14, 15, 16], and may be abolished by surgical disconnection of the hypothalamus and pituitary [17], suggesting that in sheep, the prolactin rhythm is commanded by the circadian system located in the hypothalamus.…”