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Hypothalamic regulatory hormones: physiological and clinical implications.

The hypothalamic regulatory hormones used for clinical studies are TRH, Gn-RH and somatostatin. In addition, as dopamine appears to be a physiological PIF, the dopamine agonists such as bromocriptine, could be considered as functional analogues of PIF. Gn-RH can be used to study the hypothalamic-pituitary gonadal relationship and to test the secretory reserve capacity of the gonadotrophs in disease states. Unfortunately Gn-RH testing discrimulates between pituitary and hypothalamic diseases only poorly. However gonadotrophin deficient men or women may be successfully treated with long-term Gn-RH with induction of puberty, potency, spermatogenesis and ovulation. Somatostatin has multiple actions in inhibiting endocrine and exocrine secretion but its actions are still being explored in diabetes. Bromocriptine, a long acting dopamine agonist (a functional analogue of PIF), suppresses prolactin and is highly effective in treating many hypogonadal states since hyperprolactinaemia is common. It also lowers growth hormone in acromegaly. TRH has provided a major, accurate, sensitive and safe test of thyroid function.

Dopamine↗

Peptidase inactivation of hypothalamic releasing hormones.

With the structural characterization of the hypothalamic hormones, luteinizing hormone-releasing hormone (LH-RH), thyrotrophin-releasing (TRH), melanocyte-stimulating hormone release-inhibiting hormine (MIH), and growth hormone release-inhibiting hormone, (GH-RIH or somatostatin), it has been possible to investigate their enzymic inactivation by peptidases which are present at various sites in the body. Enzymes may play an important part in the control of polypeptide hormone levels and the peptidases acting on these four hypothalamic hormones may regulate the amount of TRH, LH-RH, MIH and somatostatin released from the hypothalamus, or their action at the level of the pituitary and their removal from the circulation. By studying the peptidase enzymes, further information may be obtained on the physiological mechanisms controlling the secretion and actions of hypothalamic hormones, as well as on the design of analogues with increased or competitive activity.

Animals↗

Localization of hypophysiotropic neurohormones by assay of sections from various brain areas.

The results of studies of the localization of the hypothalamic hypophysiotropic factors based on their direct determination in sections or nuclear punches are described. Luteinizing hormone-releasing hormone was found in high concentrations in the median eminence-arcuate nucleus complex, in lower concentrations in the mediobasal zone of the preoptic area. In addition to these hypothalamic sites, it is present in all four periventricular organs, especially in the organum vasculosum laminae terminalis. Thyrotropin releasing hormone has a widespread distribution. High concentrations are in the median eminence, arcuate nucleus, dorsomedial nucleus, and anterior part of the ventromedial nucleus. Lower concentrations are in several other structures of the hypothalamus, preoptic area and septum, and low but measurable quantities are found in most of the structures of the brain. Somatostatin is also present in most structures of the central nervous system, with highest concentrations in the median eminence, arcuate nucleus, ventromedial nucleus and periventricular nucleus. There are indications that the ventromedial nucleus or its immediate vicinity contains growth hormone releasing factor. Prolactin releasing activity was present in the median eminence and mediobasal parts of the anterior hypothalamus, whereas prolactin inhibitory activity was in the dorsolateral parts of the anterior hypothalamus and/or preoptic area.

Animals↗

Stimulation of growth hormone release by luteinizing hormone-releasing hormone and melanocyte-stimulating hormone-release inhibiting hormone in the hypophysectomized rat bearing an ectopic pituitary.

Intrajugular administration of LHRH (0-6 and 1-2 mug) in hypophysectomized rats which received renal grafts of anterior pituitary induced a small but significant rise in plasma GH 5 and 10 min post-treatment. LHRH, at the same dose levels, was ineffective in weight-matched intact controls. MIF, at the dose of 1-2 mug, induced a slight GH rise 5 min after treatment in hypophysectomized trasnplanted rats, while it was ineffective in intact controls. Unlike the two hypothalamic peptides, alpha-MSH (0-6 and 1-2 mug) was ineffective as a GH-releaser in both transplanted and intact rats.

Animals↗

[Neuroaminergic control of anterior pituitary secretions (author's transl)].

The demonstration and identification of monoamines and of aminergic tracts in the central nervous system has permitted a study of their role in the control of the liberation of hypothalamic releasing hormones. Knowledge of the role of these hypothalamic neurohormones in the release of pituitary hormones is at present under study. The role of monoamines in the control of pituitary hormone functions depends narrowly on pharmacological methods intervening either in the synthesis of neuroamines or in their action on a specific receptor. The authors consider successively the implication of monoamines in the control of liberation of ACTH, GH, TSH, prolactin and gonadotropic hormones. The role of aminergic mechanisms in the physiology of pituitary releasing hormones forms an integral part of homeostasis. Knowledge of these mechanisms leads to a clinical study of their role in disorders of hypothalamo-pituitary function.

Acromegaly↗