Observations were made of fluid balance and vasopressin concentrations throughout the oestrous cycle of normally cyclic female rats housed under a 12 h light: 12 h darkness regime. Plasma vasopressin concentrations were found to increase progressively during the light period, falling again during the night on all days of the cycle except pro-oestrus. On this day, peak vasopressin concentrations of 3.32 +/- 0.8 pmol/l were seen between 10.00 and 12.00 h, with lower concentrations of 1.74 +/- 0.22 pmol/l being seen between 18.00 and 19.00 h. Urine flow appeared to reflect the changes in plasma vasopressin concentrations, being significantly lower during the light phase, with a small increase being seen over this period on pro-oestrus. Pituitary vasopressin concentrations were highest between 09.00 and 10.00 h and fell progressively over each of the 4 days of the oestrous cycle. The changes in pituitary content were greater than could be accounted for in terms of the alterations in the plasma concentrations of vasopressin.

Catheters were implanted into the fetal dorsalis pedis and maternal jugular veins of 6 ewes of 122–130 days gestation age. Fetal plasma arginine vasopressin (AVP) concentrations rose in the last few days before parturition from undetectable levels to values associated with response to minor stress. Similarly, AVP was frequently present in maternal plasma in the last week of gestation but was rarely detected earlier. The levels attained in the mother were somewhat lower than in the fetus.

Ghrelin and synthetic growth hormone secretagogues have diverse effects on the hypothalamus including effects on appetite and the growth hormone axis as well as on the hypothalamus-pituitary-adrenal (HPA) axis. We previously studied the effect of synthetic growth hormone secretagogues on CRH and AVP release from rat hypothalami in vitro, and now report on the effects of ghrelin on CRH and AVP release. The ghrelin protein content and ghrelin output from rat hypothalamic explants was measured using a specific novel ghrelin enzyme immunoassay. The effect of 10(-8) M to 10(-6) M ghrelin on CRH and AVP release was studied in the rat hypothalamic explants, where stimulation with des-octanoyl ghrelin was used as control. The presence of both ghrelin mRNA and protein could be shown in the rat hypothalamus. Ghrelin output was detected in the incubation fluid of rat hypothalamic explants and could be stimulated with high potassium concentrations. Our data also demonstrated a dose-dependent effect of ghrelin on both CRH and AVP release, while des-octanoylated ghrelin showed no effect on either peptide. In summary, the current data suggest that ghrelin is expressed in the hypothalamus both at RNA and the protein levels. Ghrelin stimulates the HPA axis in the rat via stimulation of both CRH, and particularly, AVP release from the hypothalamus. The local autocrine/paracrine and endocrine effects of ghrelin in the hypothalamus could influence all the hormonal systems involved in ghrelin effects, including growth hormone release, the HPA axis and appetite.

Fetal haemorrhage in exteriorized fetuses of 90 to 143 days conceptual age caused marked increases in fetal plasma ACTH and AVP with maximal values for ACTH at about 40% blood loss and maximal values for AVP with somewhat smaller losses. The rates of rise of ACTH and the maximal values of ACTH were similar to those found in a non-pregnant adult female subjected to haemorrhage. Fetal plasma growth hormones rose in 2 out of 5 animals with no consistent trend in the remainder. In 2 out of 5 animals traces of oxytocin appeared. In two older fetuses in which fetal plasma corticosteroids were determined there was a moderate rise. There was no correlation between maternal and fetal plasma levels with any of the hormones. Fetal ACTH, AVP and growth hormones levels were greatly in excess of those of the mother. Fetal pituitary concentrations of ACTH, oxytocin and neurophysin at all ages were similar to those found in the adult; AVP concentrations were somewhat less. No arginine vasotocin was detected. The high hormone content of the fetal pituitary contrasted with the appearance by light microscopy in the younger animals which showed little evidence for hormone storage. The experiments indicate that the fetal pituitary in the sheep by 90 days is able to synthesize, store and increase several hormones and that haemorrhage is a potent stimulus for the release of ACTH and AVP.

Plasma oxytocin concentrations were measured during late pregnancy, parturition and lactation in the miniature pig. Measurements were made of plasma oestradiol, oestrone and progesterone to determine whether there was any relationship between the concentrations of oxytocin and these steroids in the circulation. Plasma oxytocin concentrations were low or undetectable in late pregnancy. Rises of up to 68.8 mum./ml were seen at the time of delivery of the foetuses and at the expulsion of the placenta. The only steroid that seemed to relat to oxytocin release was progesterone. Oxytocin release was consistently seen when progesterone concentrations had fallen to below 10 ng/ml but no increase in concentration was observed while oestrone and oestradiol increased to their maximum concentrations of 3.86--11.6 and 0.43--0.70 ng/ml respectively. During lactation, when both oestrogen and progesterone concentrations were low, suckling caused the levels of oxytocin to increase to 7.4 muu./ml. These increases were greater during the first 2 weeks of lactation than later.