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Biomedical subjects

P M Jack

Publications and source records attributed to P M Jack.

13 recordsLinked to original sources
PubMed1979

Adrenocorticotropin and glucocorticoid concentrations in fetal and maternal plasma of rabbit does continuously infused with cortisol from day 21 to day 24 of gestation.

Previous studies have suggested that suppression of fetal rabbit adrenocorticotropin (ACTH) secretion results in impaired development of ACTH-specific adenylate cyclase activity. In order to test this hypothesis we measured fetal and maternal plasma ACTH, cortisol, and corticosterone concentrations in control does and does infused with 0.3 mg of cortisol/hour at 21 to 24 days of gestation. This cortisol infusion regimen significantly depressed maternal and fetal plasma ACTH and corticosterone concentrations but did not change fetal serum cortisol concentrations. These findings further support the hypothesis that fetal ACTH plays a role in the normal development of the adenylate cyclase catalytic portion of the ACTH receptor complex and adrenal differentiation during this critical period of fetal life.

Adenylyl Cyclase Inhibitors↗
PubMed1976

The development of adrenocorticotrophin-sensitive adenylate cyclase activity in the foetal rabbit adrenal: a correlated biochemical and morphological study.

Proliferation of the smooth endoplasmic reticulum, the site of some hydroxylating steroidogenic enzymes in foetal adrenocortical cells, is the first major change in the process of their differentiation into steroidogenic tissue. This was observed in our ultrastructural studies on foetal rabbit adrenals to begin at about day 19 of development. Morphological changes in the mitochondria, the site of production of other steroidogenic enzymes, occurred at about day 24. The elongated or rod-shaped forms of the earlier stages became flattened and rounded by this time, while the cristae were transformed from a flattened lamellar type of the earlier stages to the tubulo-vesicular form of the adult. Other changes observed included an increase in microvilli and in cell size, with a concomitant increase in thickness of the gland. Adenylate cyclase activity in foetal adrenal homogenates was assessed in response to sodium fluoride (NaF) and ACTH. All preparations responded to NaF. While good responses to ACTH were observed at days 24, 27, 28 and in the neonate, there was a lack of any significant response in the day 19 gland. Foetal ACTH was depressed by administration of cortisol, and the effects of this treatment on both the morphological changes and adenylate cyclase activity was reassessed. The response of foetal adrenals to ACTH was depressed by this treatment and differentiation of the mitochondria was arrested. These results suggest a circumscribed period for the development of ACTH-sensitive adenylate cyclase coinciding with the time at which final differentiation of the mitochondria is completed. Furthermore, both the differentiation of the mitochondria and the development of ACTH-sensitive adenylate cyclase in the foetal adrenal may be dependent on foetal ACTH secretion.

Adenylyl Cyclases↗
PubMed1975

Ultrastructural changes in the placenta of the ewe following foetal infusion of cortisol.

The placental changes which followed continuous infusion of cortisol into the sheep foetus in the later stages of gestation were, like the hormonal changes, broadly similar to those of spontaneous parturition. There was, however, a premature separation of foetal and maternal tissues in certain areas of the placental cotyledons, and this separation appeared to protect the foetal epithelium from the degenerative changes which normally take place in the short space of time between the birth of the lamb and the delivery of the foetal membranes. The results suggest that an experimental model in which premature labour is induced by the administration of cortisol to the foetus is probably incomplete, and that additional factors almost certainly contribute to the cascade phenomenon of spontaneous parturition.

Animals↗
PubMed1975

Effect of synthetic thyrotrophin releasing hormone on thyrotrophin and prolactin concentractions in the peripheral plasma of the pregnant ewe, lamb fetus and neonatal lamb.

Synthetic thyrotrophin releasing hormone (TRH) has been administered to pregnant ewes, chronically catheterised fetuses in the latter stages of gestation, and to newborn lambs. Both the pregnant ewe and her fetus showed marked rises in TSH and prolactin concentrations after administration of TRH. The placenta was impermeable to TRH, TSH and prolactin in both directions. The sheep fetus near term and the newborn lamb both demonstrated a considerable reserve of secretory capacity for TSH and prolactin.

Animals↗
PubMed1975

Effect of decapitation and ACTH on somatic development of the rabbit fetus.

Rabbit fetuses were decapitated, injected with ACTH or decapitated and injected with ACTH on day 24 of gestation. On day 29 the body weight and weight of the interscapular fat pad were compared with those of littermates. The weight, total DNA and weight/DNA ratio of the liver, heart and kidney were measured in experimental and control fetuses. A comparison was made between decapitated and control fetuses of the length of the hind limb bones and number of ossified vertebrae. The body weight of the decapitated or ACTH-injected fetus ranked significantly below the mean for the litter, but decapitated fetuses injected with ACTH ranked close to the litter mean. The growth retardation of the decapitated fetus was not manifest in the kidneys which were heavier and had a greater number of cells than normal, nor in the cell size of the heart, liver or kidneys which were equal to those of the heaviest fetus in the litter. Decapitation had no specific effect on ossification. Growth retardation of the ACTH-injected fetus was mirrored by different patterns of DNA and weight/DNA reduction in the three organs studied. Decapitation retards growth in body weight of the fetal rabbit which may be corrected by ACTH. It is concluded that the hypophyseal-adrenal axis plays a role in the control of normal fetal growth but that excess secretion of glucocorticoids results in stunting.

Adrenocorticotropic Hormone↗
PubMed1975

Ultrastructural studies of the rabbit placenta in the last third of gestation.

Placental attachment and the ultrastructure of the decidua and placental labyrinth have been studied in rabbits during the final third of gestation. The placenta became progressively easier to separate from the uterine wall as gestation proceeded. This ease of separation was associated with degenerative changes in the decidual tissue, but disruption of the placental labyrinth was not observed until the last 24 hr of pregnancy. Two types of decidual cells were observed; smaller uninucleate glycogen-containing cells and larger multinucleate cells with lipid inclusions. The ageing placentae exhibited increasing decidual degeneration associated with deposition of extracellular fibrous materials. Glycogen became less widely distributed over the period of study and changed from the beta- to the alpha-configuration. In contrast to the observed disruption of the decidual tissue, the placental labyrinth maintained its integrity until the final stages of pregnancy. A dramatic increase in subcellular activity was observed in the syncytiotrophoblast after 28 days of gestation.

Animals↗
PubMed1975

Development of pathways of insulin secretion in the rabbit.

Insulin release was studied in vitro using pieces of pancreas from rabbits of between 24 days gestational age and 6 weeks postnatal age. When allowance was made for the fraction of pancreas which was endocrine, 16-5mM-glucose caused increasing stimulation of insulin release as development advanced and 3-3 mM-glucose caused a similar rate of secretion at all ages. Secretion was not significantly influenced by insulin destruction in the incubation medium. Glucagon (5 mug/ml) did not stimulate insulin secretion from 24-day foetal pancreas but did so postnatally. Theophylline (1 mmol/1) stimulated insulin release at all ages and was equipotent on 24-day foetal pancreas in 3-3 or 16-5 mM-glucose. The stimulation of insulin release from 24-day foetal pancreas by 1 mM-theophylline occurred in the absence of extracellular glucose, pyruvate, fumarate and glutamate and in the presence of mannoheptulose and 2-deoxyglucose (each 3 mg/ml). Adrenaline (1 mumol/1) and diazoxide (250 mug/ml) abolished or attenuated the stimulation of insulin release by glucose, leucine plus arginine or theophylline from 24-day foetal, 1 day and 6 weeks postnatal pancreas. The stimulation of insulin release from 6-week-old pancreas by 1mM-barium was blocked by adrenaline and diazoxide but the effect became less with increasing immaturity. The experimental results illustrate some of the ways in which insulin secretion by the rabbit beta cell changes as a function of development and draw attention to the importance of glucose and cyclic adenosine monophosphate in this process.

Age Factors↗
PubMed1975

Adrenocorticotrophin and the development of insulin secretion in the rabbit foetus.

Foetal rabbits were injected with adrenocorticotrophin (ACTH), decapitated, or decapitated and injected simultaneously with ACTH or cortisol in utero on day 24 of gestation. The foetuses were killed after Caesarian section on day 29, and blood was collected for measurement of plasma insulin concentration and pancreatic tissue was obtained for incubation in physiological buffer. Insulin release from the pancreatic tissue of decapitated foetuses was significantly greater than that from the pancreas of control litter-mates when incubated in media containing 3-3mM-glucose, 16-5mM-glucose or 16-5mM-glucose plus 5 mug glucagon/ml, but was similar when the incubation medium contained 3-3 or 16-5 mM-glucose plus 1 mM-theophylline or 3-3mM-glucose plus 60 mM-potassium. The pancreata of decapitated or intact foetuses injected with ACTH did not differ significantly from control foetuses in terms of insulin release in response to glucose in vitro. The plasma insulin concentration of decapitated foetuses and decapitated foetuses injected with ACTH was raised, whereas that of intact foetuses injected with ACTH was similar to that of the control foetuses. Cortisol injection at the time of decapitation resulted in a high rate of foetal mortality. The results indicate that foetal ACTH or foetal adrenocortical secretion influences the normal development of glucose-mediated insulin secretion in the rabbit and that exogenous ACTH corrects the effect of decapitation on beta cell function in vitro but not on plasma insulin concentration.

Adrenocorticotropic Hormone↗