[Humoral defense in acute diarrhea in infants].
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Biomedical subjects
Publications and source records attributed to E Damian.
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The work was focused on the effect of the pineal extract on HDL-cholesterol alongside the effect of the same extract on serum cholesterol and testosterone in the rat under basal conditions. HDL-cholesterol is utilized in the rat, preferentially by the Leydig cells for steroidogenesis. Administration of melatonin-free pineal extract, in doses of 2 ml/day/animal along 3, 6 and 12 days caused a statistically significant decrease in HDL-cholesterol of 19, 21 and 20%, respectively. The same depressor effect occurred 4 hr following a unique injection of pineal extract (-25%, p less than 0.001). Cholesterolemia decreased significantly alongside with HDL-cholesterol (14, 18, and 16% after 3, 6 and 12 days and 18% after 4 hr). The effect of the pineal extract on testosterone tested in only two experiments was to depress it significantly by 43% after 4 hr and 45% after 6 days of treatment. The decrease in testosterone level following the decrease of its major precursor, cholesterol, is discussed.
The work presents the experimental data reported by specialty literature as well as those reported by the authoress on studying the pineal substances with antigonadotropic activity, namely the indole compounds and pineal polypeptides. The effects observed after administration of melatonin--prototype of the pineal-indole family--and of more or less purified pineal extracts are presented. The matter discussed upon is whether or not melatonin or arginine-vasotocin are the pineal hormones responsible for the complex actions induced by the pineal extracts.
The antisteroid urinary substance was checked out for its effect on LH and FSH under endogenous (castrated animal) and exogenous (administration of releasing hormone-GnRH) stimulation of the rat hypophysis. Administration of this substance partly blocked the castration induced LH and FSH serum increase by 65% and 37% respectively (p less than 0.01) and inhibited the GnRH stimulating effect depressing serum LH by 50% and FSH by 33% (p less than 0.05). In both experiments the LH and FSH content of the hypophysis was not influenced.
The effect of a melatonin-free pineal extract on acid phosphatase activity in the prostate of castrated and testosterone-treated rat was studied. Prostatic acid phosphatases in the mature rat are lysosomal and secretory, the former being inhibited by tartrate. Castration induces a decrease in the secretory phosphatases and an increase in the lysosomal ones with a subsequent increase in the tartrate-induced inhibition index. The specific activity of total acid phosphatase also rises. Administration of the pineal extract in the first 4 post-surgical days did not have a significant effect, but when it was prolonged to 7 days, it partially inhibited the effect of castration on prostatic acid phosphatase. Administration of testosterone to the castrated rat in the first 4 post-castration days, partially compensated the prostatic alterations, owing to the fact that the prostate is under the control of androgenic hormones. Administration of both pineal extract and testosterone in the first 4 post-castration days partially inhibited the effect of testosterone. The equillibrating role of the melatonin-free pineal extract and its effect in relation to the amount of time lapsed from surgery is discussed.
The antigonadotropic activity of a melatonin-free pineal extract before and after a 24 h dialysis was assessed by the mouse uterine-weight test. In both cases, the uterus-stimulating effect of HCG was inhibited, showing that after dialysis the extract not only retains its effect but that the latter is even higher. The amino acids content established by an amino acid analyzer was the same in two batches of extract obtained from two different stores of pineal powder. The analyzer also showed that the glutamic acid is the prevailing component as a free and bound amino acid in the total extract. It was also found that methionine is absent from the dialyzed extract. Qualitative analysis of the pineal extract revealed 16 amino acids and a concentration of proteins of 1.90-1.96 mg/ml. Quantitatively, the glutamic and aspartic acids, proline and glycine prevail over the other constituents. The glutamic acid concentration was over two times higher than the latter three.
This paper presents data revealing the regulating, equilibrating role of the melatonin-free pineal extract. Administration of this extract lowered statistically significant urinary 17-Ks and cholesterolemia in rabbits and cholesterolemia, hepatic cholesterol and ascorbic acid in the rat under basal conditions. When the initial values of these biochemical indices in the above mentioned animals were below the basal values established, then the pineal extract showed an effect of correction of these values increasing them toward the basal level. Under HCG stimulation total free and esterified cholesterol in the serum and testis as well as the DNA, RNA and proteins in the testicular tissue showed lower values than in the controls. Administration of the extract at the same time with HCG, corrected the HCG-induced lowering effect on these biochemical indices. Similarly, when GnRH induced a decrease and not an increase in serum LH, as expected, the pineal extract played the same regulating role causing rise of serum LH towards the initial values. In one of our experiments in which TRH induced a decrease and not an increase in serum prolactin, the pineal extract corrected this effect. These data suggest an equilibrating role played by the melatonin-free pineal extract in our researches on the pineal gland.
Administration of a melatonin-free pineal extract to hemicastrated rats in doses of 2 ml/day/animal induced a statistically significant decrease in their serum and testicular sialic acid after 3 days but not after 30 days of treatment. Unilaterally castrated rats receiving testosterone (6 injections) showed 10 days post-castration a statistically significant decrease in sialic acid in their serum and testes but not in the epididymis. Twenty-one days post-castration, time in which 11 testosterone injections were given, the sialic acid was low in the epididymis as well. Concomitant administration of testosterone and pineal extract caused a total reduction in the serum and partial reduction in the testes, of the lowering effect of testosterone on sialic acid. The return to the normal values of the serum sialic acid, to almost normal values of the testicular sialic acid and the increase over the normal values of the epididymal sialic acid shows the equilibrating role played by the pineal extract on the sialic acid in the hemicastrated rat treated with testosterone. The role of the melatonin-free pineal extract on sialic acid, a biochemical index involved in reproduction, is discussed.
Administration of 2 ml of melatonin-free pineal extract (30 mg bovine pineal powder per ml) per day per animal for 12 days caused, under basal conditions, a decrease of 31% in the testicular testosterone and 33% in the esterified cholesterol, a fraction used in testosterone biosynthesis, but did not change free cholesterol. Under stimulation with 50 UI HCG for 3 days, testicular testosterone was found to be very high, esterified cholesterol low and free cholesterol unchanged. Simultaneous administration of HCG and pineal extract showed that the latter inhibits partly the testicular response to HCG. The decrease in testosterone after pineal extract administration under exogenous HCG stimulation correlates with an increase in the esterified cholesterol fraction. The effect of the melatonin-free pineal extract on testicular testosterone synthesis in the rat is discussed.
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Administration of 2 ml/day/animal, of melatonin-free pineal extract to the rat for three days induced a significant decrease in the testicular tissue concentration of testosterone, cholesterol and ascorbic acid. A dose of 1 microgram melatonin/day/animal given for 3 days did not alter these biochemical elements implied in testicular steroidogenesis.
Partial purification of a melatonin-free extract obtained from bovine pineal and showing an antigonadotropic activity was studied. The following methods were utilized: Sephadex gel filtration, ultrafiltration, precipitation by alcohol, ammonium sulphate and trichloracetic acid. The fractions obtained by all these procedures as well as the dialysed extract were biologically tested through the mouse uterine test. The protein contents in all the substances studied were assayed by Lowry's method. The results showed that in the extract studied, the antigonadotropic activity was present both in the fraction under 10,000 and in the fraction above 10,000, the latter containing 72% of the proteins from the total extract.
Administration of the melatonin-free pineal extract to rats concomitantly receiving testosterone propionate caused partial inhibition of the ventral prostate growth induced by testosterone. Administration of the pineal extract to rats likewise caused a statistically significant decrease in the ventral prostate weight under basal conditions. The mechanism of action is discussed.
The present paper presents a number of results concerning the role of the pineal gland in reproduction. It has been demonstrated that the pineal polypeptides and a substance isolated by the author from children's urine and proved to have pineal extract-like actions, administered to laboratory animals induced the following effects: 1) inhibition of the exogenous HCG stimulating effect on mouse uterus, 2) decrease in excretion of the 17-KS of both testicular and adrenal origin, 3) decrease in the testis oxygen consumption in vitro, and 4) marked decrease of the serum and testicular testosterone. Melatonin, a pineal indole, studied in parallel did not alter the above biochemical indices. Pinealectomy produced in all the cases completely opposite effects. The effects obtained with the pineal polypeptides, the urinary antisteroid substance, and melatonin are discussed.
The study contains the data gathered with time with regard to the involvment of the pineal gland in the lipid metabolism. Thus, it has been demonstrated that administration of the pineal extract lowers serum, hepatic, adrenal and testicular cholesterol of rat and that pinealectomy causes reverse effects. Administration of melatonin did not cause significant alterations. The same pineal extract reduced cholesterolemia, biliary cholesterol and serum phospholipids in rabbits whereas the absence of the pineal gland caused an increase in cholesterolemia, total lipids and FFA. Pineal treatment reduced the major lipid components of the blood and aorta in experimental atheromatosis induced in rabbits. The results presented in this paper demonstrate the inhibiting role played by the pineal gland in the lipid metabolism.
The circadian variations of the testicular ascorbic acid and testicular cholesterol in the intact and pinealectomized rat were followed up. The results show that in both lots there are diurnal variations of these biochemical indices. Pinealectomy does not alter the values curve as concerns the testicular ascorbic acid but causes a reversal in the testicular cholesterol curve especially during the darkness period (the intact rat has an increased value of 2400 hrs whereas the pinealectomized one has the lowest value for the same hour).
The effect of a pineal treatment on the pituitary gland under exogenous stimulation with gonadotropin releasing hormone (GnRH) was assessed in the rat. A pretreatment with melatonin-free pineal extract under the above conditions caused a statistically significant decrease in the pituitary concentrations of DNA--by 21%, RNA--by 28%, proteins--by 19%, LH--by 25% and FSH--by 22%. Authors' findings show that the melatonin-free pineal extract plays a role in the metabolism of nucleic acids and pituitary proteins besides being implied in the synthesis of gonadotropic hormones.