The metabolic clearance rate, production rate and conversion ratios of oestrone in the sheep.
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Biomedical subjects
Publications and source records attributed to J R Challis.
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Maturation of the fetal hypothalamic-pituitary-axis may be an important factor in the stimulation of the onset of parturition. Recent studies have found that corticotrophin-releasing hormone (CRH), the hypothalamic component of this axis is also present in the placenta and the fetal membranes. We review the evidence demonstrating that glucocorticoids stimulate the production of CRH by these tissues towards term, and this is manifest by increases in CRH concentrations in maternal and fetal plasma and in placental extracts, and by increased abundance of CRH mRNA in the placenta. We discuss how CRH secretion by the placenta and fetal membranes is controlled. We hypothesize that CRH may be an important signal in initiating of the onset and maintenance of term labour and may also be a factor in the etiology of premature labour, through stimulation of the fetal HPA axis, and through paracrine/autocrine interactions within the placenta, fetal membranes and decidua.
Intravenous administration of equimolar doses of CRF (30 micrograms) and AVP (6 micrograms) to mature female sheep resulted in elevated plasma concentrations of ACTH and cortisol. Simultaneous administration of equimolar amounts of CRF and AVP resulted in a greater ACTH response compared with the sum of the responses to CRF or AVP given independently. Intravenous bolus administration of the endogenous opioid, Met-enkephalin (2.5 mg), and its potent and long-acting analogue, [D-Ala2,N-Phe4,Met(O)ol5]-enkephalin [FK33-824 (250 micrograms)], did not alter ACTH or cortisol secretion. Furthermore, naloxone, an opioid receptor antagonist given alone or concurrently with Met-enkephalin or FK33-824, was without effect. Pituitary-adrenal responses to CRF were unaltered by simultaneous administration of Met-enkephalin, FK33-824 or naloxone. These results suggest that in the sheep, opioid involvement in the tonic regulation of pituitary-adrenal function is absent. However, CRF and AVP may act alone or in synergy to control the release of biologically active ACTH from the sheep pituitary gland.
Insulin-like growth factor (IGF) I and II are synthesized within the placenta and are believed to play an important role in the regulation of placental growth and endocrine function. IGF bioavailability is determined at a cellular level by several specific binding proteins (IGF BPs), which are widely but selectively distributed in all developing tissues. We have used immunohistochemistry to localize IGF I and II peptides, and IGF BP-1, -2, and -3 in human placentae, fetal membranes and umbilical cord at 6-8 weeks after therapeutic termination and at term after spontaneous delivery. Primary antisera were directed against human IGF I, human IGF BP-1, bovine IGF BP-2, and human IGF BP-3 respectively. Immunoreactive IGF BP-2 was found in association with the syncytiotrophoblast, intermediate trophoblasts of the fetal villi and chorion, amnion and decidua; while weaker staining was seen in some but not all cytotrophoblasts. A similar but less intense staining pattern was observed for IGF BP-1 and IGF peptides in placenta and amnio-chorion. Strong immuno-staining for IGF BP-1 was seen in decidual cells. No immunoreactive IGF BP-3 was found in placenta or membranes. A co-distribution of IGF BP-2, BP-1 and IGF peptides in placenta suggests a role for these IGF BPs in determining the localization of the IGFs for actions on target tissues.