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M J Obregon

Publications and source records attributed to M J Obregon.

32 records · Page 2Linked to original sources
PubMed1982

Are iodine-deficient rats euthyroid?

Inhabitants of many severe endemic goiter areas have low serum T4 and high circulating TSH, despite normal levels of T3. This situation may be produced experimentally chronically feeding rats a low iodine diet (LID). We fed rats a Remington-type LID and gave them 1% NaClO4 in their drinking water for 2 days. After this, the animals were divided into three groups. One group was fed LID, supplemented with 5 micrograms I/rat.day and was used as the control group. Another group was fed LID alone. The third group was fed LID and given 1% NaClO4 to drink. The latter treatment was used to induce severe hypothyroidism. Animals were killed 1, 2, 3, and 5 weeks after the onset of these treatment schedules. The following measurements were made on some or all groups of animals: body and thyroid weights; thyroidal I content; soluble labeled iodoprotein profile; thyroidal labeled iodoamino acid distribution pattern; plasma T4, T3, and TSH; pituitary GH content; and liver intramitochondrial alpha-glycerophosphate dehydrogenase and cytosolic malic enzyme activities. T4 and T3 concentrations were also measured in liver nuclei of the animals killed 5 weeks after the onset of treatment. As assessed from various indices of thyroid function, the LID rats became iodine deficient, although not as markedly as those given LID and ClO4-, The plasma T4 decreased to undetectable levels, and plasma TSH increased, whereas circulating T3 remained normal throughout in the LID rats. In rats given LID and ClO4-, plasma T4 decreased sooner than in rats given LID alone; plasma T3 levels also became undetectable, and TSH increased more markedly and sooner than in rats given LID alone. As measured at the end of 5 weeks of treatment, pituitary GH content, and liver alpha-glycerophosphate dehydrogenase and malic enzyme activities were lower in rats given LID than in the euthyroid LID- and I--treated controls. They were not, however, as markedly reduced as in the severely hypothyroid LID- and ClO4--treated rats. In spite of normal plasma T3 levels, the concentration of T3 in liver nuclei of the rats given LID alone was significantly lower than that of the LID- and I--treated controls. The results show that the thyrotrophs, somatotrophs, and livers of rats given LID alone are not like those of euthyroid rats despite normal circulating T3 levels. In iodine-deficient rats, there is a discrepancy between the measured indices of thyroid hormone action in the liver and the circulating T3 level, but not between biological activity and liver nuclear T3 concentration. It remains to be seen whether the same is true in the anterior pituitary.

Animals↗
PubMed1982

Indications for and limitations of laparoscopic ovarian biopsy.

A series of 213 patients with different menstrual patterns underwent laparoscopic visualization of the ovaries and ovarian biopsy in order to evaluate ovarian function. Menstrual patterns were classified in four groups: regular menstrual cycles, oligoamenorrhea, secondary amenorrhea and primary amenorrhea. Laparoscopic gross ovarian appearance was classified in four groups, also. Microscopic picture of the ovaries was also placed in four categories. Laparoscopic vision of the ovaries is not justified in regular menstrual cycle patients. Laparoscopic vision of the ovaries might be useful when menstrual disorders exist, especially in secondary amenorrhea. There is some controversy about whether primary amenorrhea patients should be biopsied. Histology may be important in x,y karyotype primary amenorrhea. Biopsy should be avoided in oligoamenorrhea patients. Premature menopause might be diagnosed histologically in patients with secondary amenorrhea. Gross ovarian appearance may help in the selection of patients for ovarian biopsy. Sclerocystic polycystic ovaries should be biopsied, but the procedure must be bloodless and correctly performed. Streak gonad biopsy is not without hazard, and ureteral injury has been reported. The diagnostic, prognostic and therapeutic value of ovarian biopsy should be balanced against the risk and expense of the procedure.

Amenorrhea↗
PubMed1981

Presence of L-thyroxine and 3,5,3'-triiodo-L-thyronine in tissues from thyroidectomized rats.

Female rats were killed 15 days, 2 months, and 4 months after surgical thyroidectomy that was followed by injection of 100 microCi 131I. The concentrations of T3 and T4 were measured in tissues (liver, kidney, brain, heart, and hindleg muscle) specific RIAs. Results were compared to those found in intact rats. Thyroidectomy resulted in severe hypothyroidism by 2 and 4 months after the operation, as assessed by undetectable levels of T4 and T3 in unextracted plasma, high circulating TSH, hypothermia, stasis of body weight increase, and depletion of pituitary GH content. Concentrations of T4 and T3 in plasma, as determined after extraction and concentration, were very low, being less than 5% of the normal value by the earliest observation period (15 days). In contrast, although tissue concentrations and total organ contents also decreased after thyroidectomy, they were still clearly detectable 4 months after thyroidectomy. The rates of decrease of T4 and T3 concentrations in most tissues were markedly slower than expected from their rapid decrease in plasma. Some tissues still contained 20% of the normal level 2-4 months after ablation of the thyroid. Tissue levels of thyroid hormones were hardly detectable in rats thyroidectomized 6 months before, having decreased in most tissues to less than 5% of the normal value. Several animals from this group had died. It is concluded that tissues from severely hypothyroid thyroidectomized rats may contain higher concentrations of T4 and T3 than previously thought. The idea that thyroid hormone is not essential for life, based on the assumption that thyroidectomized animals survive without thyroid hormones, might have to be reevaluated.

Animals↗
PubMed1981

A survey of schoolchildren from a severe endemic goitre area in Spain.

All the boys and girls between six and fourteen years old regularly attending school in three villages from an area in Spain known ass Las Hurdes were studied with respect to thyroid size, body weight and height. Casual urine samples were obtained for the determination of iodine and creatine concentrations. Capillary blood was spotted on filter paper and used for the determination of thyroxine and thyrotropin by radioimmunoassay. The same survey was carried out in 354 school children from Madrid, whose data were used as a reference of the adequacy of the methods employed in Las Hurdes. Goitre prevalence was very high, the overall frequency being 86 per cent. The concentration of iodine in the urine was less than 20 micrograms/1 in 71 per cent of the school children. The concentration of creatine in the urine was also half that found in children from Madrid, and the daily creatine excretion in children from Las Hurdes was lower than expected from their body weight. Their somatic development, as measured by height and weight, was retarded markedly, both as compared to the Madrid reference group and to international charts. Serum T4 was less than 78 nmol/l ( micrograms/kl) in 46 per cent, of the children from Hurdes, and serum TSH greater than 7.5 mU/l in 40 per cent. A relatively low stature (below the 10th percentile) was associated with either a low serum T4, an elevated serum TSH, or both, in 30 per cent of the children. These results indicate that the persistence of endemic goitre in Las Hurdes is of great significance and that there is a continuing risk of the birth of cretins. Observations made a decade earlier in the same area show that the goitre endemic is not diminishing, and that an iodization programme is urgently needed. It also appears that a high proportion of the "normal' schoolchildren have features found in hypothyroidism.

Adolescent↗
PubMed1981

Evaluation of free and total L-thyroxine in serum by a commercial procedure.

We assessed a commercial kit (Corning Medical) for "free" and total thyroxine determination, results being compared to those obtained by the Ekins and Ellis dialysis method (free thyroxine) and the method of Weeke and Orskov (total thyroxine). The kit procedure permits determination of both free and total thyroxine within 4 to 5 h, and the combined results may disclose changes in binding to plasma proteins that would be missed if only free thyroxine were determined. With both free-thyroxine methods, the values distinguished hyperthyroid patients from normal controls and pregnant women with 100% accuracy, but there was some overlap between hypothyroid patients and controls. Absolute values with the kit procedure often exceed those obtained by dialysis, especially for hypothyroid patients and pregnant women. We conclude that the kit may be of as much diagnostic value as the dialysis method if the limitations regarding absolute values are kept in mind and the test is not used as a substitute for thyrotropin determinations in cases of suspected hypothyroidism.

Blood Chemical Analysis↗
PubMed1980

Evidence against a major role of L-thyroxine at the pituitary level: studies in rats treated with iopanoic acid (telepaque).

To determine whether T4 has an intrinsic effect at the pituitary level, it would be important to block conversion of T4 to T3 completely. We have attempted to achieve this with iopanoic acid (IOP), a radiographic contrast agent. We have then measured in the same animals the effects of such treatment on the conversion of T4 to T3 or on the deiodination of T3 and on the pituitary response to a dose of T4 or T3. Plasma TSH levels and pituitary GH content were measured as biological end points. Thyroidectomized rats were injected with a single dose of T4 (1.7 micrograms/100 g BW) labeled with [125I]T4 (Exp A) or with a single dose of T3 (0.33 microgram/100 g BW) labeled with [125I]T3 (Exp B) and treated with IOP or solvent. Animals of Exp A were killed 24 h after iodothyronine injection and those of Exp B were killed 4, 12, and 24 h after injection of the iodothyronine. The concentrations of [125I]T4 and [125I]T3 were measured in several tissues, including the anterior pituitary, after extraction and paper chromatography and quantified with the aid of 131I-labeled markers added in vitro. Plasma and pituitary T3 and T4 plasma TSH, and pituitary GH were measured by specific RIAs. Results show that treatment with IOP markedly inhibits the conversion of T4 to T3 and the deiodination of T3. In IOP-treated thyroidectomized rats, the injection of T4 results in little, if any, effect at the pituitary level, despite an almost 3-fold increase in the percentage of injected T4 found in the gland. Treatment with IOP does not inhibit the effects of a T3 dose; if anything, they appear to be enhanced. It is concluded that, as assessed from biological responses involving the anterior pituitary, a dose of T4 has little if any effect other than that which can be attributed to the T3 generated from it.

Animals↗
PubMed1979

Exchange of triiodothyronine derived from thyroxine with circulating triiodothyronine as studied in the rat.

At present it is widely assumed that T3 derived from T4 is rapidly and totally exchangeable within the volume of distribution of T3 secreted by the thyroid into the bloodstream. This concept is implied when conclusions are drawn from comparisons between a biological effect in a responsive tissue and circulating T3 and T4 levels. Such conclusions are often in conflict with those derived by comparing the biological effect with the concentrations of T3 and T4 in the responsive tissue itself. Thus, it appeared important to test the above assumption directly. Thyroidectomized rats have been treated for 4-4 1/2 days with a mixture of 131I labelled T4 (131T4) and 125I labelled T3 (125T3), which was either injected twice daily or administered by continuous i.v. infusion. The rats were bled, perfused, and their plasma and tissues submitted to extraction and paper chromatography. If the tested assumption were correct, the ratio between the T3 derived from T4 and the T3 injected as such (namely, the 131T3/125T3 ratio) should be the same in plasma, liver, kidney, heart, muscle, etc. It was evident that the 131T3/125T3 ratio was not the same for different tissues. The differences were not merely due to artefactual deiodinations. The presence of small amounts of 131I and 125I containing compounds in the T3 spot was considered as highly unlikely, though not totally excluded. The data thus suggest that T3 derived from T4 and the injected (or thyroidally secreted) T3 might not be totally exchangeable within an observation period which is considerably longer than the one for which complete equilibrium was previously assumed. If so, changes in the size of the T4 pool, or in the rate of T4 conversion to T3, might affect the concentration of T3 in a given tissue to an extent not disclosed from the circulating T3 levels alone. Several possible consequences of the present findings are discussed.

Animals↗
PubMed1979

Effects of thyroid hormones on liver binding sites for human growth hormone, as studied in the rat.

Several weeks after thyroidectomy (T), female rats stopped growing, and their pituitary GH content had decreased to less than 2--3% of the values found for age-matched controls (C). The liver membranes of such animals were explored with human GH (hGH). It was found that in the severely hypothyroid T rat, the number, but not the affinity, of the lactogenic binding sites was markedly reduced. Treatment of these rats for 3 weeks with 1.75 micrograms or T4 or 0.5 micrograms T3/100 g body weight/day restored growth, increased pituitary GH content and restored the number of liver lactogenic binding sites were practically to normal. As regards the lactogenic binding sites, similar results were obtained when the severely hypothyroid rats were treated with a much lower T4 dose (0.2 microgram/100 g/day): this dose was clearly growth promoting, and restored to normal both the low circulating GH levels and the pituitary PRL content of the severely hypothyroid rat. The changes in plasma PRL were not clear. The lactogenic binding sites on liver membranes from rats which were both thyroidectomized and hypophysectomized were decreased in number. Treatment with 0.5 microgram T3/100 g/day for 30 days (but not for 12 days) resulted in an increase in the number of lactogenic binding sites, though it did not affect growth or the undetectable plasma GH levels. The effect on the lactogenic binding sites was less marked than in T rats with an intact pituitary. It would appear that minute amounts of thyroid hormones are needed for maintenance of liver lactogenic binding sites; it is possible that this not only occurs through mechanism(s) which involve the pituitary, but also through others which do not. The possible role of these receptors in growth processes is not yet clearly understood.

Animals↗
PubMed1979

Tyrosine hydroxylase and the conversion of L-thyroxine into 3',3,5-triiodo-L-thyronone in the rat.

We have studied the effects of alpha-methyl-p-tyrosine (alpha-MPT), an inhibitor of tyrosine hydroxylase, on the in vivo conversion of L-T4 (T4) to 3',3,5-triiodo-L-thyronine (T3), and on the biological effectiveness of T4. Thyroidectomized rats were used and were injected daily with T4 maintenance doses. Three different types of experiments were carred out. The first involved isotopic equilibration with 125I-labeled T4 and measurement of urinary 125I excretion. The second series involved the injection of a single dose of [125I]T4, with the amounts of [125I]T3 in different tissues being studied 7 or 20 h later. The third series involved daily treatment for 13 days with T4 and alpha-MPT, at the end of ehich the liver alpha-glycerophosphate dehydrogenase activity was measured as a parameter of the biological effects of the hormone. Though the experimental approaches used clearly disclosed the well known effects of 6-propyl-2-thiouracil, no clear-cut effects of alpha-MPT were observed. It is concluded that alpha-MPT neither inhibits the conversion of T4 to T3 in vivo in rats nor affects the biological potency of a given dose of T4, at least to an extent compararble to that observed when 6-propyl-2-thiouracil is used. Thus, present results do not support the hypothesis that tyrosine hydroxylase is involved in the extrathyroidal deiodination of T4 to T3.

Animals↗
PubMed1978

Concentrations of triiodo-L-thyronine in the plasma and tissues of normal rats, as determined by radioimmunoassay: comparison with results obtained by an isotopic equilibrium technique.

The concentrations of T3 (3',3,5-triiodo-L-thyronine) have been determined by RIA in plasma, liver, kidney, heart, muscle, brain, and lungs of normal male rats. The method involves homogenization, addition of a high specific activity labeled T3 tracer, extraction with ethanol, separation by paper chromatography, elution of the labeled T3 spot, evaporation of an aliquot, and assay of its T3 content by a highly sensitive RIA. In order to validate the results thus obtained, they were compared with the T3 concentrations determined for the same samples using an isotopic equilibrium technique. The data obtained by RIA were in close agreement with those derived from the isotopic equilibrium technique, whenever the latter could be applied accurately. The present RIA method permits the determination of T3 in tissues without imposing the well known limitations of the isotopic equilibrium technique. The concentration of T3 was higher in the kidney than in the liver. In kidney, liver, brain, and lung, it was higher than the concentration in plasma. The concentration of T3 in heart was the same as that in plasma. Similarities and differences with respect to data reported by others are discussed.

Animals↗
PubMedDate not supplied

Specific uptake of human growth hormone by the liver of severely hypothyroid rats.

Severe thyroid hormone deficiency results in marked impairment of body growth. This is due, at least in part, to impaired growth hormone (GH) synthesis. We hae studied the possible effects of severe thyroid hormone deficiency on liver receptors for GH and for prolactin (PRL) by an in vivo technique. Female thyroidectomized (T) rats and age-paired controls (C) were injected iv with tracer amounts of biologically active monoiodinated hGH, alone or together with 200 micrograms/100 g bw of native hGH, bGH or oPRL. The liver uptake of labelled compounds, and the liver to serum radioactivity ratio was measured 20 min later. The liver to serum radioactivity ratio of C rats was decreased both by native bGH (purely somatogenic) and native oPRL (purely lactogenic). That of the T rats could only decrease with bGH. Such results confirm data obtained in vitro indicating that in the severely hypothyroid rat liver there is a marked decrease in lactogenic binding and strongly suggest that specific binding of growth hormone by the liver is not similarly affected.

Animals↗