Corticosterone treatment of pregnant low dose endotoxin-treated rats: inhibition of the inflammatory response.

Problem: Can the endotoxin-induced inflammatory response, underlying experimental pre-eclampsia, in pregnant rats be inhibited by corticosterone?

Method Of Study: On day 10 of pregnancy, rats were implanted with pellets containing 25% corticosterone and 75% cholesterol (n = 10) or with 100% cholesterol-pellets (n = 10). On day 14 of pregnancy, rats were infused with either endotoxin (1.0 microg/kg bw) or saline.

Interaction of late pregnancy and lactation in rats.

The effect of pregnancy on lactation was studied during the third week of lactational pregnancy in postpartum pregnant rats with a delay in implantation of only 1 day (1d-LP rats). In an experimental design in which the suckling litter was prevented from consuming solid food, lactational performance was estimated by weighing the ten-pup suckling litters on days 16-21 of lactation or by measuring maternal weight loss after a nursing spell on day 21. In 1d-LP rats, food consumption as well as lactational performance was lower than it was in nonpregnant lactating rats (L rats) and pregnant-lactating rats with a normal long delay of implantation of at least 6 days (LP rats).

FSH inhibits the augmentation by oestradiol of the pituitary responsiveness to GnRH in the female rat.

The effect of follicle stimulating hormone (FSH) treatment on the pituitary response to gonadotrophin-releasing hormone (GnRH) was studied in rats in various reproductive conditions. A 3-day treatment of cycling rats with FSH (Metrodin; 10 IU/injection) lowered the spontaneous pre-ovulatory. LH-surge and suppressed the pituitary luteinizing hormone (LH) response to GnRH.

Progesterone stimulates pancreatic cell proliferation in vivo.

Treatment of cyclic and pregnant rats with progesterone stimulates cell proliferation within the islets of Langerhans. It was investigated whether this effect of progesterone depends on sex and/or the presence of the gonads or the presence of oestradiol. For this purpose, Silastic tubes containing progesterone were inserted s.

Effects of food restriction on glucose tolerance, insulin secretion, and islet-cell proliferation in pregnant rats.

Pregnancy is associated with increased glucose-stimulated insulin secretion and increased pancreatic islet-cell proliferation. In the present study it was investigated whether increased food intake, as occurs during pregnancy, is involved in the regulation of these phenomena. From Day 0 of pregnancy, rats received each day the mean amount of food they consumed daily during the estrous cycle prior to conception.

Proliferation of pancreatic islet-cells in cyclic and pregnant rats after treatment with progesterone.

The effect of progesterone (P) on pancreatic islet-cell proliferation and function of cyclic and pregnant rats was investigated in vivo. Silastic tubes containing P were inserted s.c.

Glucose consumption by various tissues in pregnant rats: effects of a 6-day euglycaemic hyperinsulinaemic clamp.

In the course of pregnancy maternal tissues become increasingly more insensitive to insulin. As 6 days of euglycaemic hyperinsulinaemic clamping, from day 8 until 14 of gestation, ameliorates total glucose consumption, we analysed the contribution of individual tissues in this phenomenon. We measured not only glucose consumption, but also concentrations of the glucose transporter protein GLUT4 in selected tissues.

Role of increased insulin demand in the adaptation of the endocrine pancreas to pregnancy.

During gestation the demand for insulin increases due to a decrease in insulin sensitivity of the maternal tissues. Simultaneously, pancreatic islet-cell proliferation, as well as insulin production and secretion increase. Both phenomena appear to be caused by the actions of pregnancy hormones.

Role of gonadotrophin releasing hormone baseline concentrations in the control of pituitary gonadotrophin and ovarian steroid secretion in the pseudopregnant rat.

To study the effect of moderately elevated gonadotrophin releasing hormone (GnRH) baseline concentrations during the luteal and the follicular phase, pseudopregnant rats were infused s.c. with GnRH at several doses for 5 days.

Effect of insulin on endocrine pancreas function during late pregnancy in the rat.

To partly or completely satisfy the increasing demand for insulin, pregnant rats were infused SC with human insulin (2.4 or 4.8 IU/day) from day 14 to day 20 of gestation.

Pancreatic beta-cell function and islet-cell proliferation: effect of hyperinsulinaemia.

Pancreatic beta-cell function was studied in adult female rats, in which endogenous insulin demand was fully met by SC infusion of human insulin (4.8 IU/24 h) for 6 days, resulting in hyperinsulinaemia and severe hypoglycaemia. The amount of pancreatic endocrine tissue declined by 40%, (pro)insulin mRNA, as determined by in situ hybridisation by 95%, and the amount of stored insulin by 90%.

Arginine stimulated glucagon and insulin secretion by islets of Langerhans of pregnant and lactating rats.

Glucagon secretion by isolated pancreatic rat islets was not affected by an increase of the glucose concentration from 2.5 to 5.0 mM, but was stimulated by 25 mM arginine.

Effect of the TRH analogue, CG 3703, on prolactin secretion in the pseudopregnant rat.

The effect of the TRH analogue, CG 3703 (AG), on secretion of prolactin (Prl) was studied in pseudopregnant rats. AG stimulated Prl secretion of incubated pituitary glands in the presence of 5.10(-8) M dopamine (DA) but not in the presence of 0 or 10(-6) M DA.

Dopamine and TRH-induced prolactin secretion in pseudopregnant rats.

The stimulatory effect of TRH on prolactin (Pr1) secretion by the anterior pituitary gland (APG) of the pseudopregnant (PSP) rat was studied in vivo and in vitro. TRH, 500 micrograms, did not increase Pr1 release during the Pr1 peaks which are generated daily between 01.00 and 12.

Metabolism of pregnant-lactating rats is adapted to pregnancy rather than to lactation.

In pregnant-lactating rats implantation was induced on day 4 of lactation so that, as an exception, lactation coincided with the period of high fetal growth. The already present suckling litters of these animals lagged behind in growth, but the "second" litters were at birth normal in size and weight. Such pregnant-lactating rats were tested in vivo with intravenous glucose loads and compared with cyclic and lactating rats.

Regulation of peripheral glucagon concentrations in cyclic, pregnant, and lactating rats.

In the rat, peripheral glucagon concentrations were studied throughout pregnancy and lactation. Basal glucose concentrations were decreased during late pregnancy and during lactation, but basal glucagon concentrations were not affected. Infusion of glucose (7.

Effect of in vivo pre-treatment with oestradiol and either GnRH, GnRH agonistic analog or GnRH antagonistic analog on GnRH-stimulated secretion of LH in vitro.

In vivo treatment with GnRH or with GnRH agonistic analog (AG), but not with GnRH antagonistic analog (ANT), depleted the LH stores of the rat pituitary gland. This depletion was potentiated by oestradiol. Oestradiol augmented the in vitro LH response of the pituitary gland to GnRH.

Effects of luteolysis during late pregnancy on pituitary responsiveness to gonadotrophin-releasing hormone in the rat.

We investigated whether the increase in the gonadotrophin response to gonadotrophin-releasing hormone (GnRH) during the last days of pregnancy and the occurrence of parturition on day 22 of pregnancy in rats are due to the increase in the plasma concentrations of oestradiol-17 beta after luteolysis, which occurs around day 20. In a first series of experiments we studied the effects of s.c.

Differential effect of estrogen on pituitary responsiveness to GnRH in women with different forms of hypothalamic amenorrhea.

The effect of treatment with estradiol valerate (6 days, 2-6 mg/day) on basal levels of LH and FSH and on response of LH and FSH levels to GnRH challenge (2 X 25 micrograms GnRH, iv) were investigated in women with "hypothalamic amenorrhea", but without other endocrine disorders. Three groups were studied: 11 women with primary amenorrhea, 10 women exhibiting secondary amenorrhea related with weight loss, and 7 women with normal weight and with amenorrhea persisting after a period of severe weight loss. Before treatment with estradiol valerate the estradiol concentrations in all women were at the lower limit of the follicular phase of a normal ovulatory cycle.

Glucose and insulin responses during mixed meals or infusion of glucose in pregnant and lactating rats.

We studied the glucose tolerance in freely moving rats throughout pregnancy and lactation and during the first week after weaning. Dioestrous virgin rats served as controls. Basal glucose and insulin levels were determined after a 2-hr fasting period.

Experimental endotoxemia in pregnancy: in situ glomerular microthrombus formation associated with impaired glomerular adenosine diphosphatase activity.

The mechanism of increased sensitivity for endotoxin in pregnancy as reflected by the formation of microthrombi in renal glomeruli is unknown. It has been shown that reduced glomerular diphosphatase (ADPase) activity in the rat kidney greatly increases the intraglomerular thrombotic tendency. We now studied experimental intraglomerular thrombosis ex vivo in association with glomerular ADPase activity in pregnant and nonpregnant control rats after infusion of either endotoxin or saline solution.

Interdependence of oestradiol and 5 alpha-dihydrotestosterone in modulating LH and FSH secretion in rats.

The effects of oestradiol, 5 alpha-dihydrotestosterone (DHT) and oestradiol plus DHT on pituitary responsiveness to LHRH were studied. Rats ovariectomized for 2 weeks were infused s.c.