Hormone-treated Rats Research Articles

Hormone-induced system A amino acid transport activity in rat liver plasma membrane and Golgi vesicles. Evidence for a differential sensitivity to inactivation by N-ethylmaleimide during carrier maturation.

We have investigated the biogenesis and processing of the rat hepatic System A amino acid carrier following induction of its de novo synthesis by the combined action of glucagon and dexamethasone. Golgi subfractions isolated from hormone-treated rat liver form transport competent vesicles and possess characteristic System A activity based on pH sensitivity and 2-(methylamino)isobutyric acid inhibition of Na(+)-dependent 2-aminoisobutyric acid uptake. We have monitored the time course for appearance of the newly synthesized carrier in the Golgi and plasma membrane fractions after the administration of hormones. Our data suggest that it may also be possible to detect processing intermediates of the System A carrier in the Golgi. Perfusion of whole rat liver with 5 mM N-ethylmaleimide followed by isolation of Golgi subfractions and plasma membrane revealed a differential sensitivity such that the plasma membrane or trans Golgi activities were inactivated to a much greater extent than those of the cis or medial Golgi. In vitro N-ethylmaleimide treatment of membrane fractions isolated from an intact rat results in an inactivation of the trans Golgi and plasma membrane System A carrier protein, whereas the cis and medial Golgi fractions retained their transport activity.

Effect of L-triiodothyronine on delta 9 desaturase activity in liver microsomes of male rats.

Male rats injected with a single saturating dose of L-triiodothyronine (T3) showed, after a lag time of approximately eight hr, a sharp rise in delta 9 desaturase activity. Desaturase activity reached a plateau which was 1-1.2 times above the base line levels of rats which were not hormone-treated. The plateau was maintained for five days in animals which were kept on daily hormone-treatment. The increase in delta 9 desaturase activity by T3 required ongoing protein synthesis, because the increase in enzymatic activity due to hormone treatment was completely abolished in the presence of cycloheximide. These findings suggest that cycloheximide may block the induction of delta 9 desaturase by T3 and/or inhibit the synthesis of protein(s) essential to the desaturation-response to T3. Modifications observed in liver microsomal fatty acid composition in T3 treated rats were independent of the effect on desaturation. It is suggested that other factors, such as diet, membrane lipid synthesis and degradation, as well as fatty acid turnover and oxidation, could be involved in affecting the fatty acid composition of thyroid hormone-treated rats.

Treatment of rats with glucagon or mannoheptulose increases mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase activity and decreases succinyl-CoA content in liver

1. The activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase (EC 4.1.3.5) in extracts of rapidly frozen rat livers was doubled in animals treated in various ways to increase ketogenic flux. 2. Some 90% of the activity measured was mitochondrial, and changes in mitochondrial activity dominated changes in total enzyme activity. 3. The elevated HMG-CoA synthase activities persisted throughout the isolation of liver mitochondria. 4. Intramitochondrial succinyl-CoA content was lower in whole liver homogenates and in mitochondria isolated from animals treated with glucagon or mannoheptulose. 5. HMG-CoA synthase activity in mitochondria from both ox and rat liver was negatively correlated with intramitochondrial succinyl-CoA levels when these were manipulated artificially. Under these conditions, the differences between mitochondria from control and hormone-treated rats were abolished. 6. These findings show that glucagon can decrease intramitochondrial succinyl-CoA concentration, and that this in turn can regulate mitochondrial HMG-CoA synthase. They support the hypothesis that the formation of ketone bodies from acetyl-CoA may be regulated by the extent of succinylation of mitochondrial HMG-CoA synthase.

Changes in antizyme-ornithine decarboxylase complexes in tissues of hormone-treated rats

The presence of antizyme-ornithine decarboxylase complex in thymus and kidney of rats was demonstrated using the method of Y Murakami et al. [(1985) Biochem. J. 225, 689–697]. A very small amount of complex was found in kidney of control rats, accounting for only 1–3% of total enzyme in the tissue, while in thymus, approximately one-third of the total ornithine decarboxylase in thymus occurred as an antizyme-enzyme complex. After treatment with dexamethasone, both free ornithine decarboxylase and antizyme-ornithine decarboxylase decreased in thymus, the free enzyme activity decreasing more rapidly. In kidney, the concentration of the antizyme-ornithine decarboxylase complex increased after dexamethasone treatment, but only after the induction of free enzyme activity had reached its peak and begun to decrease. The pattern of the changes in amount of antizyme-ornithine decarboxylase complex after prolactin treatment differed from those observed in the dexamethasone-treated animals. In both kidney and thymus, the concentration of antizyme-ornithine decarboxylase complex increased concurrently with the induction of free enzyme activity. Both free and complexed ornithine decarboxylase had increased at 2.5 h after prolactin treatment and continued to increase to maximum specific activities at similar rates. In thymus, the amount of ornithine decarboxylase present as a complex reached 70% of the total in the tissue. In both thymus and kidney, the concentration of antizyme-ornithine decarboxylase complex decreased more slowly than did free enzyme activity. Free antizyme was observed only in thymus of dexamethasone-treated animals. The amount of measurable inhibitor was decreased if cycloheximide was given with dexamethasone.

The Role of Steroid Hormones and Decidual Induction in the Regulation of Adenosine Diphosphoribosyl Transferase Activity in Rat Endometrium*

Adenosine diphosphoribosyl transferase (ADPRT) activity was measured in endometrial nuclei isolated on estrus and day 4 from rats ovariectomized on estrus (day 0) and treated on days 0-3 with vehicle, estrone (E), progesterone (P), or E plus P, a treatment that supports a decidual response. Also, measures were made of ADPRT in endometrial nuclei isolated from rats during the estrous cycle, days 1-7 of pseudopregnancy, and days 5-7 of pseudopregnancy after decidual induction on day 4. E treatment produced an increase in ADPRT activity, DNA content, tissue mass, and total protein. P alone did not affect ADPRT activity or DNA content. Enzyme activity and DNA content measured after E plus P treatment were significantly lower than those after estrone treatment and higher than those in vehicle-treated controls. The parallel stimulation of ADPRT activity and DNA synthesis by E supports a role for ADPRT in cellular proliferation. The blockade of E-stimulated ADPRT activity by P is consistent with a previously proposed model of hormonal regulation of rat uterine pyridine nucleotide metabolism. In endometrium from cycling rats, ADPRT activity did not change between metestrus and proestrus, but declined on estrus. After a rise on day 1 of pseudopregnancy, ADPRT activity remained stable through day 5 and declined on day 6. The relatively constant enzyme activity during the cycle and early pseudopregnancy, when hormone levels undergo great changes, may reflect an additional level of control in intact animals not observed in ovariectomized hormone-treated rats. Decidual ADPRT activity declined on day 5, 1 day after uterine trauma, and increased on day 6. This pattern of enzyme activity is consistent with the initial phase of cytodifferentiation, followed by rapid proliferation during early decidualization.

Hybridization in situ studies of angiotensinogen gene expression in rat adrenal and lung.

Both rat adrenal and lung contain low levels of angiotensinogen mRNA, as shown by Northern blot and nuclease S1 analyses of RNA extracted from these tissues. We sought to identify the cellular localization of angiotensinogen mRNA in these two tissues using hybridization in situ of tissues obtained from both control rats and rats administered a combination of dexamethasone, ethynylestradiol, and T3. For the adrenal of hormone-treated rats, angiotensinogen mRNA was identified in periadrenal fibroblast-like cells and brown adipose tissue. For control rats, positive hybridization was obtained for fibroblast-like cells immediately adjacent to the adrenal capsule, but not for periadrenal brown adipose tissue. No hybridization was obtained for cells of the adrenal cortex, medulla, capsule or vessels. For the lung of hormone treated, but not control rats, angiotensinogen mRNA was identified in perivascular and peribronchial fibroblast-like cells and brown adipose tissue in the lung hilum. No hybridization was obtained for pulmonary parenchyma, bronchi, or vessels. These results confirm the widespread tissue distribution of angiotensinogen mRNA, and provide further evidence for the formation of angiotensin within tissues by mechanisms independent of the circulating renin-angiotensin system.

Transferrin and sulfated glycoprotein-2 messenger ribonucleic acid levels in the testis and isolated Sertoli cells of hypophysectomized rats.

Both FSH and testosterone act on Sertoli cells in the testis. It is possible that the action of these hormones on Sertoli cells results in an increased capacity for the cells to carry out their prescribed functions, among which are the synthesis and secretion of specific glycoproteins. Changes in the testicular levels of two specific mRNAs in hypophysectomized hormone-treated rats were determined by solution hybridization to cRNA probes. The mRNAs coding for transferrin and sulfated glycoprotein-2 (SGP-2), both of which are secretion products of Sertoli cells, decreased dramatically in the testis of hypophysectomized rats that were maintained for 20 days untreated with hormones. If hypophysectomy was done to rats at 20 days of age, daily injections for a subsequent 20 days with FSH or FSH in combination with testosterone partially maintained both transferrin and SGP-2 mRNA levels. Testosterone alone was ineffective in 20-day-old rats. In contrast, if hypophysectomy was performed on 40-day-old rats, daily injections of testosterone alone or in combination with FSH were most effective in maintaining higher levels of the specific mRNAs. When the Sertoli cells from rats hypophysectomized at 20 days of age were placed in cell culture, FSH again was most effective in the stimulation of transferrin mRNA above control levels. However, when the Sertoli cells from the rats hypophysectomized at 40 days of age were placed in culture, FSH was slightly stimulatory, but testosterone had no effect on the transferrin mRNA levels. Neither FSH nor testosterone affected the levels of SGP-2 mRNA in the cultured cells regardless of the age of the animal at the time of hypophysectomy. Additional in vivo studies were done in which the rats were hypophysectomized at 20 days of age, allowed to regress for 17 days, and then injected daily with hormones for 3 days. The levels of transferrin and SGP-2 mRNA in this experiment were stimulated by FSH alone or by a combination of FSH and testosterone to an extent similar to that in the cultured cells. These studies showed that FSH is most important in the younger rats and testosterone is most important in the older rats in the maintenance of specific mRNA levels. In addition, the level of stimulation observed with either hormone is different depending on whether the hormone is given in culture or in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Enhancement of carbon tetrachloride-induced liver injury by glucagon and insulin treatment.

Rats given a dose of carbon tetrachloride (CCl4) immediately received injections of glucagon and insulin every 4 h. They frequently died after 4 h and showed a significantly higher mortality between 8 h and 28 h as compared to the control rats where such deaths occurred 16 h later. At 8 h, the derangements of SGPT values and prothrombin time were significantly greater in the hormone-treated rats than in the control rats. In these CCl4-intoxicated rats, hepatic reduced glutathione content at 4 h was significantly reduced after hormone treatment. The treatment significantly enhanced CCl4 metabolism, conversion of 14CCl4 into 14CO2 in vitro, by microsomes isolated from the liver, whereas it did not affect the microsomal cytochrome P450 content. These results suggest that glucagon and insulin treatment increased CCl4 hepatotoxicity in rats through activating the cytochrome P450-dependent mono-oxygenase system. This would merit consideration for the clinical application of this treatment.

Effects of amiodarone and thyroid dysfunction on myocardial calcium, serum calcium and thyroid hormones in the rat.

1 Myocardial calcium content was found to be elevated and serum calcium reduced in hypothyroid rats. 2 Treatment of rats with amiodarone at either 30 mg kg-1 or 150 mg kg-1 daily did not result in any significant changes in myocardial or serum calcium. 3 The administration of amiodarone to hypothyroid rats attenuated the changes in serum but not myocardial calcium, suggesting that amiodarone may exert a thyroid hormone-like effect in the hypothyroid state. 4 The administration of amiodarone to thyroid hormone-treated rats resulted in attenuation of the effects on serum calcium and calculated intracellular calcium; this was consistent with an antagonistic interaction between amiodarone and thyroid hormones. 5 Administration of amiodarone resulted in significant changes in circulating thyroid hormone levels in the rat; triiodothyronine was reduced and basal thyrotrophin elevated compared to euthyroid controls. Serum thyroxine was not changed; this is in contrast to the effects in man. 6 Amiodarone does not exert its anti-arrhythmic action via changes in total myocardial calcium content in the euthyroid rat; nonetheless the described interactions between the drug and thyroid hormones may be involved in its mechanism of action.

Increase in DNA polymerase alpha activity associated with DNA synthesis due to FSH or oestrogen in ovaries of immature rats.

DNA polymerase activities and DNA content of ovaries from immature intact rats (4-29 days after birth), hypophysectomized rats and hormone-treated hypophysectomized rats were measured. During normal ovarian growth DNA polymerase alpha activity and DNA content of ovaries increased. The polymerase activity decreased gradually after hypophysectomy without any alteration in the DNA content. Administration of ovine FSH (2 micrograms/day) or oestradiol-17 beta (1 mg/day) to hypophysectomized rats enhanced ovarian DNA content and DNA polymerase alpha activity, whereas DNA polymerase beta activity did not change significantly. These results suggest that DNA polymerase alpha participates in DNA synthesis in these ovaries. The specific activity of DNA polymerase alpha (the activity per microgram DNA) in the ovaries increased between 4 and 14 days after birth, and then remained almost constant; the specific activity declined gradually after hypophysectomy. Administration of FSH or oestradiol-17 beta but not of ovine LH, progesterone or testosterone to hypophysectomized rats restored the specific activity. Mixing experiments with different kinds of ovarian extracts suggested that no activators of DNA polymerase alpha were present in the extracts. These results suggest that FSH or oestrogen causes the induction of DNA polymerase alpha accompanied by DNA synthesis during cell proliferation in ovaries of immature rats.

Kinetic studies on the stimulation of Na+-H+ exchange activity in renal brush border membranes isolated from thyroid hormone-treated rats.

Na+-H+ exchange activity in renal brush border membrane vesicles isolated from hyperthyroid rats was increased. When examined as a function of [Na+], treatment altered the initial rate of Na+ uptake by increasing Vm (hyperthyroid, 18.9 +/- 1.1 nmol Na+ X mg-1 X 2 sec-1; normal, 8.9 +/- 0.3 nmol Na+ X mg-1 X 2 sec-1), and not the apparent affinity KNa+ (hyperthyroid, 7.3 +/- 1.7 mM; normal, 6.5 +/- 0.9 mM). When examined as a function of [H+] and at a subsaturating [Na+] (1 mM), hyperthyroidism resulted in the proportional increase in Na+ uptake at every intravesicular pH measured. A positive cooperative effect on Na+ uptake was found with increased intravesicular acidity in vesicles from both normal and hyperthyroid rats. When the data were analyzed by the Hill equation, it was found that hyperthyroidism did not change the n (hyperthyroid, 1.2 +/- 0.06; normal, 1.2 +/- 0.07) or the [H+]0.5 (hyperthyroid, 0.39 +/- 0.08 microM; normal, 0.44 +/- 0.07 microM) but increased the apparent Vm (hyperthyroid, 1.68 +/- 0.14 nmol Na+ X mg-1 X 2 sec-1; normal 0.96 +/- 0.10 nmol Na+ X mg-1 X 2 sec-1). The uptake of Na+ in exchange for H+ in membrane vesicles from normal and hyperthyroid animals was not influenced by membrane potential. H+ translocation or debinding was rate limiting for Na+-H+ exchange since Na+-Na+ exchange activity was greater than Na+-H+ exchange activity. Hyperthyroidism caused a proportional increase and hypothyroidism caused a proportional decrease in Na+-Na+ and Na+-H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of ovarian sex steroids on osmoregulation and vasopressin secretion in the rat.

Effects of sex steroids on osmoregulation were studied in intact and ovariectomized Sprague-Dawley rats treated for 2 wk with subcutaneously implanted hormone pellets containing 0.5 mg 17 beta-estradiol (E2) alone (group 1) or combined with 50 mg progesterone (PG; group 2) and 5.0 mg E2 alone (group 3) combined with PG (group 4). An additional group (5) of animals was given 14 daily injections with 100 micrograms/100 g body weight of E2. Controls for each group received vehicle alone. There were no alterations in basal plasma osmolality (Posmol) or vasopressin (PAVP), except for group 3 in which a small (2.5 mosmol/kg) decrement in Posmol was observed. However, mean PNa was decreased (0.9-3.4 meq/l) in hormone-treated rats, and alterations in Pglucose and/or Purea could not explain the Na-osmolal discrepancy. Intraperitoneal hypertonic saline resulted in stepwise increases in both Posmol and PAVP. Regression analysis of PAVP on Posmol demonstrated similar osmotic thresholds for AVP release in estrogen and control rats, but the slope (sensitivity of the response) was significantly (P less than 0.005) greater in hormone-treated animals. In contrast, the PAVP response to isosmotic volume depletion was not altered by estrogen. The enhanced response to osmotic stimuli could not be explained by alterations in plasma volume or pituitary AVP content and differed from PAVP -Posmol relationships observed by us previously in gravid rats. In other experiments Posmol and PAVP were similar during all stages of the estrus cycle, while Posmol was approximately equal to 10 mosmol/kg lower in 21-day gravid rats. These data demonstrate that, although estradiol has little effect on basal osmoregulation or hemodynamically mediated AVP release, PAVP responses to osmotic stimuli are markedly enhanced. These osmoregulatory effects, however, differ from those observed during rodent gestation.

Completion of Schistosoma mansoni Life Cycle in Thyroidectomized Rats and Effects of Thyroid Hormone Replacement Therapy

The survival and maturation of Schistosoma mansoni worms was analyzed in normal, thyroidectomized (Thyrox), and hormone-restored Thyrox rats. Restoration therapy was conducted with both T3 and T4; weight gain of treated rats was monitored to assess hormone-replacement efficacy. Worm yields, lengths, and sex-ratios were compared. Egg yields and the capacity of miracidia to hatch from eggs were also analyzed. The results of these studies support the conclusion that the sequence of steps leading to completion of the S. mansoni life cycle are operational in Thyrox rats. Hormone-treated Thyrox rats are restored to the nonpermissive status, although the worms isolated from these rats still differ in certain respects when compared to worms isolated from normal rats.

Appearance of new hepatic glucocorticoid binding proteins under various stressful conditions: relation to endogenous glucocorticoid secretion.

When rats were subjected to the stress of burns, tumors, or partial hepatectomy, a notable new peak of glucocorticoid binding protein appeared on DEAE-cellulose chromatography. This peak accompanied the original peak, which was the only dominant peak in intact rats. The appearance of the new binding protein was concomitant with a high rise in serum corticosterone levels. The new peak was eluted with 0.12-0.14 M NaCl and another, small new peak with 0.02-0.03 M NaCl, while the original peak of intact rats was eluted with 0.05-0.08 M NaCl. In rats adrenalectomized prior to the stress, the new peaks did not appear. To mimic these stressful conditions which provoked a burst of endogenous glucocorticoid, rats were administered with an exogenous high dose of dexamethasone (100 micrograms/100 g B.W.) in vivo. The new peak eluted with 0.12-0.14 M NaCl was again observed and was more dominant in the hormone-treated rats than the stressed rats. These three peaks eluted with 0.02-0.03 M, 0.05-0.08 M, and 0.12-0.14 M NaCl are called here Peak A, B, and C, respectively. This is the first demonstration of the effect of physiological changes in serum levels of glucocorticoid hormone on the nature of glucocorticoid binding protein by DEAE-cellulose chromatography.

Increased Glucagon Receptors in Chronically Hypersomatotrophic and Hyperglucagonemic Rats

The effect of increased levels of growth hormone on glucagon binding by isolated hepatocytes and on the cellular cyclic AMP response to glucagon was evaluated in rats bearing growth hormone-secreting tumor (Mt-T-W15) and in rats treated with rat growth hormone. An increased binding, due to an increased number of receptors, was observed in both groups of animals. Glucagon binding did not correlate with plasma glucagon levels, suggesting a failure of down regulation, possibly due to an effect of growth hormone and insulin on the number of receptors. Tumor-bearing and growth hormone-treated rats had larger hepatocytes so that, when hormone binding was expressed in terms of square micrometer of membrane surface, it appeared decreased. When the tumor was removed the increase in the number of glucagon receptors per cell persisted, even though the average cell size returned toward normal. It is suggested that this retention of the receptors may have been the result of continuing hyperinsulinism. Basal cAMP levels were elevated in hepatocytes of tumor-bearing and growth hormone-treated animals, possibly due to cell hypertrophy. On the other hand, the maximum cAMP response to glucagon was not altered by the experimental procedures. A negative effect of insulin on cAMP accumulation may explain this apparent paradox. Indeed, hepatocytes isolated from rats following tumor removal, but with continuing hyperinsulinemia, had a lower maximum cAMP response, even though the glucagon binding per cell or per unit of cell surface was increased.

The influence of cigarette smoke and treatment with contraceptive hormones on the fibrinolytic activity in the rat

The fibrinolytic activity in the vessel wall (FAV), in plasma and in euglobulin solution (FAE) was determined in rats exposed to cigarette smoke in an inhalation chamber or treated with contraceptive hormones. In the smoke-exposed rats increased FAE and significantly decreased FAV were demonstrated. No effect on fibrino-lysis was recorded in the hormone-treated rats, in which mean plasma levels of ethinylestradiol and d-norgestrel were 74 pg/ml and 0.17 ng/ml, respectively, six hours after the last subcutaneous administration.

The mode of action of anabolic agents: the effect of testosterone on muscle protein metabolism in the female rat.

Testosterone (1 mg/kg body-weight per d) given subcutaneously to female rats increased their growth rate and food conversion efficiency but not their food intake compared with that of the placebo-oil controls. A higher dose of testosterone (10 mg/kg body-weight per d) failed to increase the daily weight gain. The increased growth rate of the testosterone-treated rats appeared to occur in the whole body and not specifically in muscle. There were no significant changes in body composition. The fractional synthetic rate of gastrocnemius muscle protein was higher in the hormone-treated rats than in controls. This contrasts with previous results for the anabolic agent trenbolone acetate and reflects differences in the mode of action of these two different steroids, both with androgenic properties.

Thyroxine preferentially stimulates transcription by isolated neuronal nuclei in the developing rat brain cortex

The administration of thyroxine to neonatal rats stimulates RNA synthesis by neuronal nuclei isolated from the developing rat brain cortex. Glial nuclei are relatively resistant to thyroxine treatment. The activity of neuronal RNA polymerase II is particularly stimulated by the hormone. Thyroxine also affects neuronal chromatin structure as shown by changes in the relative proportion of different subnuclear fractions obtained by gentle micrococcal nuclease digestion of nuclei from hormone-treated rats.

A quantitative analysis of the roles of dosage, sequence, and duration of estradiol and progesterone exposure in the regulation of maternal behavior in the rat.

The regulation of the onset of maternal behavior in the rat is under hormonal control. This study reports a new endocrine model for the study of the hormonal regulation of maternal responsiveness. The model employs the administration of physiological amounts of the steroids estradiol (E2) and progesterone (P) via Silastic implants to inexperienced nulliparous rats and measurement of the effects of these implants on maternal behavior. In the first two experiments, the levels of E2 and P in the sera of pregnant and hormone-treated rats were measured by RIA. Using known physiological treatments of E2 given in combination with P, the effects of E2 and P on maternal behavior were measured. Treatment with a combination of E2 at all dosages plus P for 2 weeks before P removal and behavioral testing stimulated a fast onset of maternal behavior in ovariectomized nulliparous rats. Exposure for 2 weeks to small E2 implants (1 or 2 mm; approximately 20-30 pg/ml serum) did not affect maternal responsiveness, whereas large E2 implants (10 mm; approximately 110 pg/ml serum) stimulated maternal behavior. P treatment alone had no behavioral effect. Simultaneous removal of E2 plus P before exposure to foster young also resulted in a stimulation of behavioral responsiveness, indicating that the presence of elevated titers of circulating E2 is not a requirement for stimulation to occur. In addition to facilitating a rapid onset of behavior, the quality of the response in steroid-primed rats was similar to that measured in lactating rats in a T-maze test. In another experiment, when female rats were treated with P before E2 administration, maternal behavior was rapidly induced. Thus, P itself can sensitize the female to the behavioral effects of E2. Finally, the duration of steroid-exposure before testing was found to influence maternal behavior. Increased durations of E2 plus P exposure before testing were accompanied by decreased latencies to respond maternally to foster young. These data indicate that during pregnancy, E2 and P prime the female to respond to her young at birth. The intensity of the steroidal priming increases as pregnancy progresses, and this primed potential is subsequently unmasked by the decline in P and the maintenance of E2 secretion around parturition. These findings demonstrate that behavioral processes can be modified in the adult animal as a result of long term changes in endocrine state, i.e. pregnancy.

Developmental Transition of Alkaline Phosphatase from Suckling to Adult Type in Rat Small Intestine: Molecular Species and Effect of Injected Cortisone and Thyroxine<xref ref-type="fn" rid="fn1"><sup>1</sup></xref>

Postnatal change of rat intestinal alkaline phosphatase from suckling to adult type occurred at the weaning stage (Uezato et al. (1981) Biochem. Int. 2, 561). Two distinct forms were observed in suckling rat small intestine. One was soluble and the other was membrane-bound. The ratio of the soluble to the membrane-bound form increased after birth until these forms were replaced by the adult type, which consisted of membrane-bound forms different from that of sucklings. The soluble form was demonstrated almost exclusively during the suckling period and was distributed in the distal third of the small intestine. The postnatal increase of alkaline phosphatase was enhanced by administration of hormones such as cortisone and thyroxine. On the other hand, acid β-galactosidase activity in the distal segment was reduced rapidly by the same treatment. The change of alkaline phosphatase from suckling to adult type was accelerated by the injected hormones. In the distal segment the ratio of soluble to membrane-bound activity in the homogenate prematurely decreased after administration of the hormones. Between 16 and 18 days of age, alkaline phosphatase of hormone-treated rat small intestine changed completely from fetal-suckling type to typical adult type in both the proximal and distal segments.