Leon Hellman

The relationship of sleep and sleep stages to neuroendocrine secretion and biological rhythms in man.

Publisher Summary This chapter reviews the major new observations made regarding the temporal organization of the 24-hour pattern of hypothalamic-pituitary function in regard to sleepwaking function. It discusses the recent application of these results to certain clinical disorders. All the pituitary hormones studied with the technique of frequent plasma sampling have been found to be secreted in an episodic manner throughout the 24-hour day. These hormones have important temporal secretory pattern relationships with the sleepwaking 24-hour cycle. In addition, the sleep stage cyclic pattern during nocturnal sleep is closely related to the timing of several pituitary hormones indicating state control by the central nervous system (CNS) over the timing and amount of secretion under normal physiological conditions. Each system appears to have its own temporal organization and response to manipulations of the sleepwaking cycle, and no single principle or mechanism can be invoked to explain these differing patterns. The concept that a homesotatic steady state or basal level is present for any extended time period of the 24-hour day is clearly not the case. The data suggest that a major mechanism of control takes place by CNS 24-hour temporal programs that initiate secretion independent of existing plasma concentrations under normal stable conditions.

Luteinizing hormone: Changes in secretory pattern during sleep in adult women

Abstract Plasma samples were collected every twenty minutes from each of five normal women and luteinizing hormone was measured by radio-immunoassay. Plasma concentrations of luteinizing hormone were decreased in the first part of the sleep period with the maximum drop occuring during the third hour following stage II onset. Analysis of similar data from a group of five normal men revealed no significant differences in the LH secretory pattern between waking activity and sleep or between the two halves of the sleep period. Analogy was made with the differential capacity of the hypothalamus in males and females to release LH cyclically. Speculation was offered on the possible role of the pineal gland in the sleep-related changes of LH secretion in women.

Twenty-four-hour patterns of luteinizing hormone secretion in humans: ontogenetic and sexual considerations.

Publisher Summary This chapter discusses the 24-hr patterns of luteinizing hormone secretion in humans. Much progress is made in recent years in understanding factors controlling gonadotropin secretion in humans. This progress is made possible primarily by three technical advances: (1) the development of sensitive and specific assays for LH (luteinizing hormone) and FSH (follicle-stimulating hormone), especially radio immunoassay; (2) frequent blood sampling by techniques that interfere as little as possible with the subjects waking and sleeping activity; and (3) polygraphic recording of the EEG (electroencephalogram), EOG (electrooculogram), and EMG (electromyogram) during sleep so that sleep onset and offset can be precisely determined and correlations can be made with sleep stages. Using the methods enumerated in the foregoing paragraph, we will describe findings from this laboratory which deal with 24-hr LH secretory patterns in men and women from childhood to adulthood. The twenty-four-hour patterns of LH (luteinizing hormone) secretion are characterized by major changes with ontogenetic development and by marked gender differences. Thus, sleeping activity is distinguished during puberty by an augmentation of LH secretion while, conversely, LH secretion decreases during the sleep of adult women. Adult men do not show such sleep-related changes in LH secretion.

Recent advances in human steroid metabolism.

Publisher Summary This chapter discusses steroid metabolism that concern either recent developments in analytic techniques or interpretations of complex endocrine laboratory data. It is frequently pertinent to determine accurately the production rate (PR) of a steroid hormone. “Production rate” is defined as the sum of the glandular secretion of a particular hormone plus all other compounds that contribute to this hormone or to the metabolites measured. In the past, the PR has been approximated or inferred from the measurements of urinary metabolite levels or blood levels. The urinary metabolite levels only approximate actual glandular production because of unpredictable alterations in metabolism, difficulties in hydrolysis of urinary steroid conjugates, and the fact that several precursors can yield the same metabolites. In an attempt to relate steroid blood levels to production rate, variations are produced by circadian rhythms and alterations in metabolic clearance rate. Thus, attention has shifted to the more direct measurement of steroid production rates using isotopic methods.

Cortisol metabolism in the morning and evening; relation to cortisol secretion rate measurements

Abstract The question was studied whether the discrepancies observed in cortisol secretion rate determinations from several metabolites were due to changes in metabolic pathway of cortisol during the course of the day. Cortisol-4- 14 C was administered to two subjects in the morning at about 0800 hr. The studies were repeated in the same subjects twice in the evening at about 1800 hr and one subject received cortisol-4- 14 C at 1415 hr as well. The specific activities of 6 metabolites were determined and the apparent cortisol secretion rates were calculated. The production rates from the various metabolites were not in precise agreement at any of the times of day studied; the disagreement was apparently greatest when the tracer was given in the evening. That the time of day at which labeled cortisol is injected is not the factor responsible for the different estimates was shown in an adrenalectomized subject maintained on dexamethasone. Tracer cortisol-4- 14 C was given to this patient at 1750 hr and 36 hours later another tracer of cortisol 1,2- 3 H was given at 0900 hr. Complete urine collections were obtained from the time of administration of the first tracer until 36 hours after the second. The urine was processed as a single collection. The 3 H/ 14 C ratios of all the metabolites were identical demonstrating that the labeled cortisol followed identical metabolic pathway in the morning and in the evening. It thus appears that a diurnal variation in cortisol metabolizing enzymes is not responsible for the demonstrated discrepancies between metabolites when secretion rate is measured by the isotope dilution method from urinary metabolites.