Erlio Gurpide

Interpretation of Tracer Data: Significance of the Number of Terms in Specific Activity Functions

It has already been shown that the number of pools in an open system in the steady state cannot be determined from the number of exponential terms in the specific activity function of a pool, even if the data were free from experimental error. However, some information is conveyed by the number of exponential terms. The information is different depending upon whether the data are obtained from the pool into which the tracer is introduced or from another pool. In the latter case, the number of exponential terms is shown to indicate the maximum number of intermediate pools involved in the shortest path of transfer of material from the injected pool to the pool in question. With regard to the former case, this paper is restricted to functions with two exponential terms and shows which systems of n pools (n >/= 2) are consistent with such data. Consequently, biexponential experimental curves can be interpreted in terms of models consisting of an unrestricted number of pools in which each pool is defined in terms of fast mixing. The generalization to cases of functions with more than two exponential terms can be carried out in a similar manner.

Estimation of secretory rates of hormones from the specific activities of metabolites which have multiple secreted precursors

The calculation of rates of entry of material into an open system of multiple pools in the steady state from the specific activities of end products, which may be derived from several pools, is described. This analysis may be applied to estimate the rates of secretion of steroid hormones from the specific activities of urinary metabolites which may have various hormones as common precursors. In a previous publication (Gurpideet al., 1963) formulae have been presented by which secretory rates could be calculated after a single injection of the tracers assuming that each of the urinary metabolites was uniquely derived from one of the pools in the system. In the present article similar formulae were derived without this assumption. Consequently, it is shown that, under certain circumstances, non-uniquely derived metabolites can be used to estimate secretory rates, and that it may be unnecessary to consider the pathways of conversion of the hormones to the metabolites or the sites where these conversion occur.

Utilization of ingested dehydro-isoandrosterone sulfate for the production of estrogens by normal and adrenalectomized pregnant subjects

In pregnancy estrogen precursors are normally converted to estrogens in the placenta. Dehydroisoandrosterone sulfate (DS) was chosen for this study because it is an effective precursor of estrogens in pregnancy. Subjects were 2 normal pregnant women 1 bilaterally adrenalectomized patient who was pregnant and 1 normal nonpregnant women. Oral administration of carbon-14 labeled or of unlabeled DS and iv injection of tritiated DS were used. Sources of reagents and details of methods are given. The isotope ratios of urniary DS and the decrease in the specific activity of this metabolite with the ingestion of DS indicated that over 60% of the ingested steroid entered the bloodstream. Placental conversion of DS to estrogens was not reduced by the increased amounts of circulating DS. Therefore a significant increase in the rate of production and urinary excretion of estrogens resulted. The adrenalectomized pregnant patient at term had increased her subnormal rate of production of estrone plus estradiol from 5 mg/day to 16 mg/day by ingesting 60 mg of DS daily. It is concluded that an effective increase in estrogen production in pregnant women can be achieved by oral administration of DS. The bulk of the ingested steroid was transferred to the maternal circulation and aromatized in the placenta. Therefore ingestion of DS is a convenient means of generating estrone and estradiol which may be available to the fetus.

Interpretation of tracer data: Some factors which reduce the number of terms in the specific activity functions inn-pool systems

The number of exponential terms in the function which describes the change in the specific activity of a pool following the injection of an isotopically labeled tracer is usually considered to equal the number of pools in which the labeled compound is distributed. However, the number of exponential terms may be smaller than the actual number of pools in the system, even if all pools exchange material with each other. This study is concerned with the derivation of relationships among the fractional rates of transfer between pools which are necessary and sufficient for a reduction in the number of exponential terms for all exchanging pools. The concept of linear dependence among the specific activity functions is basic to this analysis. By considering these relationships, it is possible to interpret the data on the basis of models consisting of a large number of pools which satisfy the condition of fast internal mixing. Such models may be necessary for a meaningful interpretation of tracer data obtained from biological systems.

Evaluation of rates of secretion and of interconversion of steroid hormones.

The amount of a steroid produced per day is usually evaluated by methods which measure the disposition of an isotopically labeled tracer of the hormone (injected intravenously) by following the decline in the specific activity of the hormone in blood [1] or by determining the cumulative specific activity of a urinary metabolite of the hormone [2,3,4]. In the application of these methods it has been assumed that they provide a measure of the dilution of the tracer by the endogenously secreted hormone. In this article, situations will be described in which the measurement of the dilution of the injected tracer of the hormone would not be sufficient to evaluate its rate of secretion. Such situations may arise when the hormone is produced not only by secretion but also by peripheral conversion from other precursors, or when the produced hormone does not mix completely with the injected tracer and does not have the same metabolic fate. In these situations it is convenient to correlate the fate of the administered isotope with that of the endogenously secreted hormone by considering models consisting of interrelated “compartments” or “pools.” A pool is defined by both a compound and the space in which it is distributed. A compound or a tracer entering a pool is assumed to mix immediately with the entire pool. The calculation of rates of entry of material into each pool or rates of transfer from one pool to another is dependent on the chosen models. Some conclusions obtained from tracer analysis of open systems of multiple pools at the steady state are presented in this article where it will be shown that the simultaneous administration of more than one tracer can make possible the evaluation of the secretory rates of a hormone in situations in which. that information cannot be obtained by administering only one tracer of the hormone. The mathematical proofs of statements made in this article are given in a paper in the Journal of Clinical Endocrinology and Metabolism [5].