Measurement of hormones

Hormonal levels fluctuate significantly in normal animals thus, hormonal change is not a highly sensitive indicator of reproductive toxicity. However, greater sensitivity can be obtained if multiple measurements of hormonal levels are made if carefully evaluated throughout the estrous cycle, significant alterations can indicate an adverse reproductive effect. 

For their work on hypothalamic hormones, Schally and Guillemin shared the Nobel Prize in Physiology or Medicine in 1977, along with Rosalyn Yalow, who (with Solomon A. Berson) developed the extraordinarily sensitive radioimmunoassay (RIA) for peptide hormones and used it to study hormone action. RIA revolutionized hormone research by making possible the rapid, quantitative, and specific measurement of hormones in minute amounts. 

The measurement of hormonal secretion during night sleep and the parallel assessment of sleep EEG provide substantial evidence for a mutual relationship between sleep EEG pattern and nocturnal hormonal secretion. In this context, CRH plays a major role but other hormones and neuropeptides are also involved, e.g. growth hormone (GH), which is released from the pituitary under the control of the hypothalamic growth hormone-releasing hormone (GHRH). 

CRITICAL ASSESSMENT OF THE METHOD Changes in pituitary hormone contents are frequently characteristic and may be followed up by measurement of hormone secretion profiles if required. Analytical methods for the rat are often also applicable to mice. For toxicology studies in dogs, preparation of the pituitary glands at autopsy may be performed, but is time-consuming and less advisable because of the small numbers of animals in such studies. 

At the end of the treatment period, the animals are killed by decapitation, preferably 24 hours after the last treatment injection. Body weight and organ weights are recorded, and organs of interest are dissected out at autopsy for histological examination and/or measurement of hormone contents. 

An extension of enzyme immunoassay is the enzyme affinity assay applicable to studies of nonimmunological interactions. This is already exemplified by the measurement of hormone using its receptor and by our studies on the interaction of fibronectin with collagen. - Assays of these and similar principles might well become a new area of expression for EIA. 

With the introduction and use of monoclonal antibodies, the measurement of hormones is now accurate and precise. The production of hormones in cancer involves two separate routes. First, the endocrine tissue that normally produces it can produce excess amounts of a hormone. Second, a hormone may be produced at a distant site by a non-endocrine tissue that normally does not produce the hormone. The latter condition is called ectopic syndrome. For example, the production of adrenocorticotropic hormone (ACTH) is norraotopic by the pituitary and is ectopic by the small cell of the lung. Consequently, elevation of a given hormone is not diagnostic of a specific tumor, because a hormone may be produced by a variety of cancers. 

Box 25-1 lists the clinical conditions in which hormones that regulate glucose, namely insulin, proinsulin, C-peptide, and glucagon, have been measured. Although there is interest in the possible clinical value of measurement of the concentrations of insulin and its precursors, the assays are useful primarily for research purposes. There is no role for routine testing for insulin, proinsulin, or C-peptide in patients with diabetes mellitus. It must be emphasized that the diagnostic criteria for diabetes mellitus do not include measurements of hormones, which remain predominantly research tools. 

Seth R, Motte P, Kehely A, Wimalawansa SJ, Wimalawansa S, Self CH, et al. The development of a two-site enzyme immunometric assay (EIA) for calcitonin and its application in the measurement of hormone in normal subjects, MTC patients and postmenopausal women. Horm Metab Res 1989 21 3-5. 

The lowered detection limits of the newer two-site immunoassays for the measurement of pituitary hormones now make it possible to distinguish an abnormally low value from the lower end of the normal reference interval. Although assessment of a particular aspect of pituitary function should also include clinical signs and symptoms of hormone deficiency and the measurement of hormones secreted by the pertinent endocrine gland (e.g., T4, cortisol, and testosterone), the newer, ultrasensitive assays for TSH, FSH, LH, and ACTH allow for an accurate distinction of a true low result from low normal. A scheme for testing of pituitary reserve is fisted in Box 50-6. 

Vining R, McGinley R. The measurement of hormones in saliva Possibilities and pitfalls. J Steroid Biochem 1987 27 81-94. 

Serum total T4 concentrations were initially determined indirectly, using methods that measured the amount of iodine in a protein precipitate of serum (protein-bound iodine, PBI). In addition to hormonal iodine, the PBI tests also measured iodoproteins, iodotyrosines, inorganic iodine, and thyroglobulin. More specific T4 procedures involved the measurement of hormonal iodine in either a butanol extract of a serum protein precipitate (butanol-extractable iodine) or in a purified fraction of serum (I4 by column). These methods were useful because the iodine in T4 normally accounts for 80% to 90% of all iodine in serum. Both... 

An attractive possibility is that stimuli which affect plant growth and development act on the systems which control endogenous amounts of lAA, and thus the stimulus is transduced into the appropriate growth or developmental response. The tropic responses and the development of secondary vascular tissue are examples of situations where careful measurement of hormone levels have shown that the levels of lAA are playing an important part in bringing about a specific response. 

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