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Biomedical subjects

S J Henning

Publications and source records attributed to S J Henning.

At least 55 records · Page 3Linked to original sources

Kinetics of circulating corticosterone in infant rats.

Corticosterone plays an important role in the regulation of postnatal development in the rat. Basal concentrations of plasma corticosterone increase markedly during the 3rd wk of life. To date, however, the physiologic bases of this increase have remained unclear. To understand the determinants of circulating concentrations of corticosterone during this period, the plasma half-life of disappearance at steady state (t1/2), the apparent volume of distribution, and metabolic clearance rate were determined after injection of a tracer dose of 3H-corticosterone in rats at 12, 16, and 22 days of age. The t1/2 for total plasma corticosterone decreased with increasing age. The volume of distribution decreased even more steeply and, consequently, the MCR displayed a highly significant decline between 12 and 22 days of age. As plasma concentrations of corticosteroid-binding globulin are known to increase markedly during this period, the t1/2 of protein-bound corticosterone was measured and that of free corticosterone was computed. At all ages the t1/2 of bound corticosterone was less than that of free corticosterone. Protein binding of the injected 3H-corticosterone increased significantly with development. Thus, increased binding of corticosterone is associated with decreased t1/2. The increasing association of corticosterone with corticosteroid-binding globulin during this developmental period is the most likely explanation for the steep decline of volume of distribution and thus of the metabolic clearance rate for corticosterone. The latter provides, for the first time, an understanding of the basis of the developmental increase in plasma concentrations of corticosterone.

Aging↗

Effects of diabetes on development of small intestinal enzymes of infant rats.

The effect of streptozotocin (SZ) on the development of small intestinal enzymes in postnatal rat pups was studied. SZ was injected ip on Day 10 and, if necessary, again on Day 12. On Days 15, 18, and 21, one pup from each group (including a vehicle-injected control (C) group) was decapitated under conditions which minimized stress. Plasma glucose, insulin (IRI), and corticosterone were measured, as were pancreatic IRI, liver glycogen, and liver membrane binding of IRI. Small intestinal segments were processed and analyzed for sucrase, lactase, maltase, and ileal acid beta-galactosidase activities. Our results indicate that plasma glucocorticoid levels remained virtually constant in both SZ and C groups, while the ontogenic profiles of sucrase and maltase in SZ rats were shifted toward an earlier appearance and a precocious maturation. Circulating levels of IRI were not reduced significantly by SZ despite the fact that pancreatic IRI was decreased 95%. Jejunal lactase, unlike data reported for diabetic rats, was not affected by SZ diabetes. Also, acid beta-galactosidase was unaltered in the SZ rat pups. It is concluded that possibly the elevated disaccharidases seen in diabetic postnatal rat pups are the direct effect of elevated blood glucose. If so, the SZ rat pup model may be a useful tool with which to study effects of glucose on intestinal enzymes in the absence of changes in plasma insulin.

Animals↗

Intestinal accumulation of lead salts and milk lead by suckling rats.

Absorption of lead is known to be enhanced during infancy. In this study, the sites of intestinal accumulation of Pb by suckling rats have been determined under various conditions using 203Pb as a tracer. When 203Pb was administered intragastrically (IG) as a soluble salt, accumulation occurred primarily in the duodenum, regardless of dose and vehicle. In contrast, when rat pups suckled from a dam which had received 203Pb, the only region of the small intestine showing accumulation of radioactivity was the ileum. To confirm that these differences were not related to the route of administration, rat milk was labeled with 203Pb and was then used for IG administration. Once again, accumulation (4 hr post-administration) was confined to the ileum. When the dose was increased 10-fold, milk Pb displayed some accumulation in duodenal tissue, but very much less than that of soluble Pb at the same time and dosage. At 20 hr postadministration, there was negligible 203Pb in any region of the small intestine following administration as a soluble salt, but substantial retention in ileal tissue following administration in milk. The strikingly different patterns of intestinal accumulation obtained with Pb salts as compared with milk Pb suggest different modes of absorption of Pb ingested in these two forms.

Animals↗

Mammary resistance: a possible controlling factor in milk ejection.

At 8 and 13 days post partum, rats have the same total milk availability; yet, in response to suckling they release a greater amount of milk on day 13 than on day 8. Increased sensitivity to suckling in the more advanced lactators may result from a greater release of oxytocin or from changes in the mammary glands as lactation advances. The present study explores this latter possibility in anaesthetized dams at 8-9 and 13-15 days of lactation. Milk release and intramammary pressure were measured in anaesthetized dams in response to various doses of oxytoxin. Milk release was determined from the body weight gain of pups which had been fasted for 5 h before suckling on dams which had been isolated for 5 h. This parameter was significantly greater in 13- to 15-day lactators than in 8- to 9-day lactators over the range of oxytocin doses examined. In contrast, intramammary peak pressure and its dissipation time were significantly larger in the 8- to 9-day lactators than in the 13- to 15-day lactators. The compliance of the mammary glands was indirectly assessed at the two stages of lactation. When a constant pressure pulse was introduced into a cannulated gland, the resulting pressure peak was significantly greater in 8-day than in 13-day lactators, indicating a greater resistance in the former. Taken together, these results indicate that when endogenous oxytocin is inhibited (by anaesthesia) the greater milk release observed at the later stage of lactation in response to various doses of oxytocin may be due to a decline in mammary resistance as lactation progresses.

Animals↗

Control of protein intake in the young rat.

Both adult and weanling rats are able to control their dietary intake of protein. The purposes of the current study were to determine: the precision of this ability in the weanling rat and when this ability makes its ontogenic appearance. We studied three overlapping age groups spanning the third, fourth and fifth postnatal weeks. Animals chose between two isocaloric liquid diets, one protein-free and the other composed of 50% protein. The intake volume of each diet was measured daily. Three days after introduction to the diets, pups were subjected to short-term tests designed to determine their ability to distinguish between the two diets. All three age groups responded to the protein conditions. However, the youngest group displayed comparatively weaker responses characterized by a prolonged period of reduced protein intake and weaker responses to the protein conditions of the short-term test. We conclude that young rats control protein intake by the end of the third postnatal week and that this ability strengthens throughout the remainder of the weaning period.

Aging↗

Circulating corticosterone in the infant rat: the mechanism of age and thyroxine effects.

Infant rats exhibit a marked rise in serum concentrations of corticosterone between postnatal days 12 and 24. As this rise appears to be cued by L-thyroxine, the aim of the current study was to determine the physiological bases of the effects of both age and thyroid status on serum corticosterone. The in vivo response to either adrenocorticotropic hormone (60 mU/g body weight) or dibutyryl 3',5'-cyclic adenylate (0.3 mg/g body weight) increased between 10 and 16 days and was advanced and delayed by hyper- and hypothyroidism, respectively. In contrast, in vitro studies with adrenals from rats aged 10 and 16 days showed no effect of age on either basal or adrenocorticotropic hormone-stimulated production of corticosterone. Chronic administration of exogenous corticosterone to hyperthyroid animals resulted in significantly higher concentrations of serum corticosterone than did an identical administration to hypothyroid animals. As hyperthyroidism was associated with marked elevations in the concentration of corticosteroid-binding globulin and in the extent of binding of corticosterone, these results suggest that the effects of both age and thyroid status on serum concentrations of corticosterone may reflect changes in the metabolic clearance of the hormone.

Adrenal Glands↗

Postnatal development of cholesterol ester hydrolase activity in the rat adrenal.

In certain circumstances the activity of cholesterol ester hydrolase (CEH) activity is believed to be rate-limiting for corticosterone production by the adrenal. The principal aim of the current study was to determine whether the activity of CEH displays a developmental increase in the infant rat which could, in part, account for the marked increase in serum corticosterone which begins at the end of the second postnatal week. The data show that the specific activity of CEH (units/mg cytosolic protein) during development is actually a mirror image of the pattern seen for serum corticosterone, i.e. CEH activities are high when serum corticosterone concentrations are low and then fall when serum corticosterone is rising. Even when total activities of CEH in the adrenal were calculated, there was no increase in parallel with the initial rise of serum corticosterone. At each age studied, stressed pups displayed significant increases of serum corticosterone; however, their CEH activities were no different from those in the non-stressed littermates. It is concluded that the activity of CEH is not the rate-determining factor for the developmental surge of basal concentrations of serum corticosterone nor for stress-induced elevation of corticosterone during the developmental period. A second aim of the current study was to address the more general question of whether steroidogenesis in the developing adrenal is limited by substrate supply. Measurement of the cholesterol content of adrenal mitochondria showed no ontogenic increase, suggesting that substrate supply, from any source, is not rate-limiting for steroidogenesis at these ages.

Adrenal Glands↗

Investigation of the nature of the "stretch response" in suckling rats.

The "stretch response" in suckling rats has commonly been used as an index of milk ejection and milk intake. In the current study, we have compared the behavior of pups suckling on dams with either full, empty or ligated mammary glands. In response to an IV bolus of oxytocin, pups suckling on both full and empty nipples displayed the characteristic stretch behavior. Lack of milk release from the latter nipples was confirmed by lack of weight gain by the pups. In contrast to pups suckling on intact nipples, those suckling on ligated nipples did not display the stretch response. It is concluded that this behavior occurs in response to erection of the nipple and is not necessarily associated with milk release.

Animal Population Groups↗

Basis for lactose aversion in the weanling rat.

As reported previously, weanling rats will choose to consume more of a liquid diet composed of 12% lactose (low-L) than of an isocaloric liquid diet composed of 47% lactose (high-L) despite the greater sweetness of the latter diet. To investigate the basis for this, saccharin was added to the high-L diet to overwhelm any unpalatable qualities. The results of several choice tests indicate that pups initially prefer the saccharin-sweetened diet. However, if the low-L diet is the alternate choice, the preference shifts to the low-L diet after several days of exposure. This initial preference for the sweetened high-L diet suggests that the high lactose aversion is due to post-ingestive consequences rather than to low palatability of the high-L diet. Furthermore, it appears that the aversion to a high concentration of lactose takes precedence over a preference for the increased sweetness of the high-L diet.

Animals↗

Effect of propylthiouracil dose on serum thyroxine, growth, and weaning in young rats.

The antithyroid drug propylthiouracil (PTU) is a potent inducer of hypothyroidism in the rat. To evaluate the effects of PTU on serum thyroxine (T4) concentration, growth, and weaning progression during development, five doses of PTU (0.0001, 0.0005, 0.001, 0.005, and 0.01 g/100 ml) were administered to infant rats via drinking water of the dam. The highest dose, 0.01%, is commonly used in developmental studies. The results indicate that 0.001% PTU creates hypothyroid pups without the debilitating characteristics of pups raised on 0.01% PTU. A second experiment examined the effects of 0.001% PTU on serum T4 concentration, growth, and weaning progression during the fourth postnatal week. Serum T4 concentration was depressed throughout the study period to 25% of controls. The hypothyroid pups continued to grow, although they were significantly smaller than untreated controls. Weaning was initiated by postnatal day 22 and completed on day 29. For normal untreated pups, weaning is initiated by day 17 and completed by day 26. Thus hypothyroidism delays but does not abolish the weaning process.

Animal Population Groups↗

Role of thyroxine in the postnatal development of rat hepatic tryptophan oxygenase and ornithine aminotransferase.

The activities of tryptophan oxygenase and ornithine aminotransferase are known to increase markedly in rat liver during the postnatal period. The aim of this study was to determine whether thyroxine regulates the development of these two enzymes. It was found that hyperthyroidism had no effect on the activity of tryptophan oxygenase, but caused a modest increase of ornithine aminotransferase activity at 10 days of age. The latter effect persisted in adrenalectomized animals, indicating that it was not secondary to elevation of plasma corticosterone. When thyroxine was administered together with cortisone acetate, elevation of ornithine aminotransferase activity was substantially greater than that observed with cortisone acetate alone. It is concluded that the postnatal development of hepatic ornithine aminotransferase is primarily controlled by glucocorticoids, but that the effect of these hormones may be potentiated by thyroxine.

Adrenalectomy↗

Regulation of milk ingestion in the infant rat.

The aim of this study was to differentiate between maternal and offspring factors involved in the control of milk ingestion. Specifically, we investigated: (1) the temporal pattern of milk ingestion in fasted and non-fasted sucklings; (2) the amount of milk released as compared to that of milk available; and (3) the roles of the age of pups and the lactational stage of the dam as determinants of milk release. There were three general findings. First, the temporal pattern of milk letdown following a 5-hr accumulation consisted of an initial rapid phase followed by a slow "maintenance" phase. Second, a limiting factor in the amount of milk released is the dam's sensitivity to the suckling stimulus which changes as lactation progresses. Third, the age of the pups does not appear to play a determining role in milk release, but the degree of their deprivation does. In summary, it is suggested that compensation for weight loss during a fast in infant rats depends on an interplay between the pups' ability to increase their own intake, the milk availability, and the maternal sensitivity to suckling.

Age Factors↗

Enzymic development of the small intestine: are glucocorticoids necessary?

The aim of this study was to determine the extent to which the postnatal maturation of intestinal hydrolases in the rat is dependent on the developmental rise of circulating corticosterone that occurs at the end of the 2nd wk of life. Pups were adrenalectomized (adX) on day 9 (i.e., before the developmental surge of corticosterone begins) and were killed on days 17, 20, 23, and 26. Serum corticosterone was measured to eliminate any incompletely adX animals. The rates of the developmental increases of sucrase and maltase activities and the developmental decreases of lactase and acid beta-galactosidase activities were depressed in adX pups aged 23 days and younger as compared with sham-operated controls. Administration of corticosterone (10 micrograms X g body wt-1 X day-1) to adX pups restored the developmental changes of these enzyme activities to rates equal to or greater than those in the sham-operated pups. By 26 days of age, all four enzyme activities of adX pups had reached their normal ontogenic plateau. We conclude that adrenal corticosteroids are potent determinants of the rate of developmental changes of intestinal hydrolases but that these hormones are not necessary for enzymes to eventually reach adult activities.

Adrenalectomy↗

Role of dietary preferences in the weaning pattern of the rat.

Weaning in the rat begins on postnatal day 17 and is completed by day 26. To evaluate the contribution of dietary preferences and/or aversions to weaning progression, choice experiments utilizing isocaloric liquid diets were conducted. In experiment 1, both consumption records and behavioral studies showed that pups choosing between two diets differing only in the nature of the carbohydrate (CHO) (glucose vs. lactose) had a strong preference for the glucose diet. In experiment 2, pups chose between diets differing in the relative proportions of CHO and fat. When the CHO was glucose, the preference was for the high-CHO diet, whereas when the CHO was lactose, the preference was for the low-CHO diet. The sweetness preference and/or lactose aversion of these experiments was present from day 17 onward and therefore cannot explain the gradual transition seen in normal weaning. In experiment 3, behavioral testing showed that pups choosing between suckling from their anesthetized dam or drinking a liquid diet strongly preferred to suckle at day 17 but to drink by day 24. The gradual transition displayed in this experiment suggests that the decline of interest in suckling plays an important role in the process of weaning.

Animals↗

Duodenal uptake of lead by suckling and weanling rats.

The aim of the current study was to determine the site of absorption of Pb by suckling rats. When 203PbCl2 (carrier-free) plus Pb-acetate (50 micrograms/g BW) was intragastrically administered to rat pups aged 10 and 14 days, mucosal uptake of Pb, measured 2 h after intubation, was manyfold greater in the duodenum than in other regions of the small intestine. By 24 days of age, this duodenal uptake was no longer apparent. In suckling pups the duodenal content of Pb became undetectable by 24 h postintubation; in contrast, ileal uptake was minimal at 2 h but increased progressively through 24 h. The ileal uptake component was also age-dependent, having disappeared by 24 days of age. These findings suggest that it is the duodenum where Pb absorption occurs, whereas ileal uptake represents intestinal retention. To assess the role of the milk diet in the elevated Pb absorption by the duodenum of suckling animals, the effect of fasting following intubation was determined. The duodenal uptake of Pb was substantially higher in fasted pups than in suckled littermates. Correspondingly, blood Pb levels were more than 4-fold higher in fasted pups than in suckled pups. We conclude that the enhanced absorption of Pb in the suckling rat is due to duodenal absorption and that this absorptive process is even further enhanced in the absence of milk.

Animals↗

Development of suckling controls in the rat: independence from thyroxine.

Until 2 weeks of age, rat pups attach to the nipples of their dam with the same avidity regardless of whether they are fed or fasted. During the 3rd postnatal week, some mode of control of suckling appears such that fasted pups attach much more rapidly than fed pups. In this study we have investigated the effects of hyper- and hypothyroidism on the maturation of suckling controls. Surprisingly, the results indicate that this aspect of behavioral development is independent of the thyroxine status of the pup. We conclude that the maturation of suckling controls is not cued by the developmental rise of serum thyroxine that occurs during the 2nd postnatal week.

Animals↗