Endocrine Reviews

Frohman, Lawrence, A.;Jansson,, John-Olov

1986 Endocrine Reviews

doi: 10.1210/edrv-7-3-223pmid: 2874984

I. Introduction THE PERIOD of time spanning the interval between the first postulate of the existence of a GH-releasing hormone (GRH) and the reports of its isolation and sequence encompassed more than two decades. In retrospect, several factors accounted for the exceedingly long interval. Most important were the requirement for development of new technology for both chemical purification and bioassay, the complexity of the stucture of GRH as compared to other releasing hormones, the susceptibility of GRH to biological inactivation during purification procedures, and the small quantities of hormone present in animal hypothalamus as compared with other hypophysiotropic hormones. However, once the sequence was identified, the rate of accumulation of knowledge concerning the biology of this hormone was extraordinarily rapid, resulting in information about the structure of its gene complex, the mechanisms of GRH action, the regulation of its secretion, and its potential use in treating both humans and animals. This review will address several of the above aspects of GRH, including the historical factors related to its isolation. We will also discuss extrapituitary actions of GRH, pathogenetic aspects of altered GRH secretion, and similarities and differences between GRH and other hypothalamic releasing hormones. This content is only available as a PDF. Author notes * Studies performed in the authors' laboratory were supported in part by USPHS Grant AM-30667 and by a grant from the Swedish Medical Research Council (to J-O. J). Copyright © 1986 by The Endocrine Society

Durant,, Sylvie;Duval,, Dominique;Homo-Delarche,, Françoise

1986 Endocrine Reviews

doi: 10.1210/edrv-7-3-254pmid: 2427332

IT IS well established that glucocorticoids exert catabolic effects on connective tissue and delay wound healing. They induce skin atrophy partly by decreasing the proliferative capacity of skin fibroblasts and the synthesis of the ground substance. Despite extensive investigations, the mechanisms of these in vivo steroid effects remain a matter of controversy, since the studies performed to elucidate the actions of adrenal steroids on the proliferation of various types of fibroblasts in vitro have led to contradictory results. Some authors have indeed described an inhibition of the proliferation of fibroblast cultures treated with glucocorticoids, whereas others have reported a stimulatory action of these drugs on cell division. In the present paper, we have attempted to present a comprehensive review of the data and thus provide an explanation for the differences observed among in vitro experiments. In fact, many of the reported discrepancies may be due, in part, to the use of different experimental models, of different experimental schedules and culture conditions, and to the various methods employed to monitor cell proliferation. Moreover, the complexity of the actions of glucocorticoids in vivo may be explained by the demonstration that, in addition to their metabolic effects on fibroblasts, glucocorticoids also indirectly affect fibroblast proliferation by controlling the syntheses or actions of various factors produced by other cell types. This content is only available as a PDF. Copyright © 1986 by The Endocrine Society

Hutson, J., M.;Donahoe, P., K.

1986 Endocrine Reviews

doi: 10.1210/edrv-7-3-270pmid: 2874985

IT HAS BEEN assumed for the last 50 yr that testicular descent is under hormonal control. The exact mechanism has remained unknown, although the general belief in recent years has been that descent is mediated by androgens. Postnatal rodents have provided a convenient model, since descent is incomplete at birth and can be influenced by both exogenous androgens or antiandrogens. Moreover, fetal mice exposed to estrogens have undescended testes, and the inhibitory effect of estrogens can be prevented by simultaneous injection of human CG. These studies have been interpreted as demonstrating inhibition or stimulation of androgen secretion, with consequent effects on testicular descent. The role of androgens has been questioned, however, because antiandrogens, such as cyproterone acetate, fail to block descent in the fetus. Recent studies of children and mice wiith complete testicular feminization associated with androgen resistance also fail to show an effect of androgens in the transabdominal phase of descent. Based on these studies, a biphasic model for the hormonal control of testicular descent has been proposed, with androgens stimulating only the second or transinguinal phase. The first phase could be controlled by Mullerian Inhibiting Substance (MIS), but this thesis remains unproven. This content is only available as a PDF. Author notes * Supported by a National Health and Medical Research Council (Australia) Fellowship in Applied Health Sciences. Copyright © 1986 by The Endocrine Society

Sapolsky, Robert, M.;Krey, Lewis, C.;McEwen, Bruce, S.

1986 Endocrine Reviews

doi: 10.1210/edrv-7-3-284pmid: 3527687

AS RECENTLY as 1900, tuberculosis, influenza, and pneumonia were the leading causes of death in our country (1). For the most part, however, these infectious diseases, as well as those of poor hygiene or undernutrition, no longer plague us. Instead, we succumb most frequently to heart disease and cancer, diseases of slow degeneration (1). Most of all, unlike so many in the generations before us, we are in a position to age. Regardless of what else occurs, we age, we become more constrained by the discrepancy between what we were and what we have become, and each step becomes harder. The goal in the study of aging is not to halt the process, because we can no more be cured of aging than of birth. The goal, instead, is to slow and soften the sharpest edges of the biological unraveling that constitutes aging. Over the past 5 yr, we have examined some of the sharpest edges of the pathology of aging. We have studied the capacity of aged organisms to respond appropriately to stress and the capacity of stress to cumulatively damage aging tissue. This content is only available as a PDF. Author notes * The studies described were made possible by a predoctoral grant from the National Institute on Aging (to R.M.S.). † Mathers Fellow of the Life Sciences Research Foundation. Copyright © 1986 by The Endocrine Society

Adler, Robert, A.

1986 Endocrine Reviews

doi: 10.1210/edrv-7-3-302pmid: 3017688

TRANSPLANTATION of the rat anterior pituitary gland to the kidney capsule results in a state of chronic hyperprolactinemia. For more than 35 yr two versions of this model have been used to study the functions of PRL. Autotransplantation of the pituitary to the kidney capsule induces hyperprolactinemia, but growth, GH secretion, and other anterior pituitary functions are diminished. Nonhypophysectomized rats implanted with anterior pituitary glands from littermate donors also have excess circulating PRL levels, but growth, GH secretion, and thyroid function remain normal. In the intact pituitary-grafted male rat, gonadal testosterone secretion is maintained despite diminished gonadotropin secretion. One shortcoming of the intact pituitary-grafted rat is glucocorticoid excess, the mechanism of which is unclear. However, adrenalectomy with adrenal steroid replacement of pituitary-grafted rats provides an animal model that appears to have one abnormality only, excess PRL secretion. This animal preparation compares favorably with other models used to study the many actions of PRL. This content is only available as a PDF. Author notes * Studies with this model have been supported by NIH Grants R01- AM-22032, K01-AM-00707, S07-RR-05392, by a Merit Review Grant from the Veterans Administration, by the A. D. Williams Fund of the Medical College of Virginia, and by a grant from Innovative Research of America. Copyright © 1986 by The Endocrine Society

Pardridge, William, M.

1986 Endocrine Reviews

doi: 10.1210/edrv-7-3-314pmid: 3017689

THERE are at least two incentives for investigating the mechanisms of transport of peptides through the brain capillary wall, i.e. the blood-brain barrier (BBB). First, it is important to understand how circulating peptides, such as insulin, insulin-like growth factors (IGFs), transferrin, angiotensinogen, PTH, or others affect the brain, and these effects must necessarily involve the interface between blood and brain. Second, the vast promise of peptides as neuropharmaceuticals has not been realized, and this is due, in large part, to the fact that virtually all of the potential peptide pharmaceuticals are water soluble and, thus, are substantially excluded from entry into brain by the BBB. However, a major purpose of this review is to emphasize that knowledge of the physiological mechanisms that mediate the transport of peptides through the BBB may lead to the development of new strategies for delivery of peptide pharmaceuticals to brain. This content is only available as a PDF. Author notes * This work was supported by NIH Grant R01-NS17701 and by the Juvenile Diabetes Foundation. Copyright © 1986 by The Endocrine Society

New, Maria, I.;Speiser, Phyllis, W.

1986 Endocrine Reviews

doi: 10.1210/edrv-7-3-331pmid: 3527688

Introduction SINCE the first known case of 21-hydroxylase deficiency (21-OHD) was reported by the Neapolitan anatomist DeCrecchio in 1865 (1), numerous investigators have unravelled the mechanisms of adrenal steroid synthesis and the associated enzyme defects responsible for congenital adrenal hyperplasia (CAH). Among the enzyme deficiency states associated with inappropriate virilism, 21-OHD is the most common. The therapeutic use of synthetic adrenocortical hormone preparations within the last 30 yr has made it possible to study the natural history of a disease which was often fatal in infancy. The last two decades have seen the application of RIA techniques to the measurement of hormonal levels in these patients, allowing differentiation between enzyme defects based on precursor-product ratios. The documentation of linkage of the 21-hydroxylase gene to the human leukocyte antigen (HLA) complex led to the elucidation of several genetic facets of the disease, including the distinct HLA markers associated with the nonclassical, or late onset, 21-OHD allele. Finally, the cloning of the genes that encode the 21-hydroxylase enzyme has provided a means of examining the specific genetic defect responsible for the various forms of CAH due to 21-OHD. This content is only available as a PDF. Author notes * Some of the work described in this review was supported by USPHS NIH Grants HD-0072 and AM-07029, the Horace Goldsmith Foundation, a Norman and Rosita Winston Foundation Research Fellowship, and by a grant (RR47) from the Division of Research Resources, General Clinical Research Centers Program, NIH. Copyright © 1986 by The Endocrine Society