Showing papers in "Recent Progress in Hormone Research in 1985"

The physiology of gonadotropin-releasing hormone (GnRH) secretion in men and women.

Abstract: Publisher Summary This chapter discusses the physiology of gonadotropin-releasing hormone (GnRH) secretion in men and women. The study of the normal physiology of GnRH secretion in the human is complicated by two features unique to neuroendocrine systems in which hypothalamic neuronal messages interface with the classical endocrine pathways. These difficulties stem from the intermittent mode of secretion of a series of evanescent releasing factors and the closed portal blood supply, which they traverse. The first approach employed to obtain an indirect assessment of GnRH secretion has been the use of frequent sampling of peripheral blood to evaluate the episodic secretion of gonadotropins. The second major approach employed to study the secretion of GnRH has been the use of various defects of GnRH release in the form of hypogonadotropic disorders. As a result of these inherent limitations of both approaches—either passive monitoring of endogenous GnRH secretion via observation of gonadotropin pulsations or active intervention with exogenous GnRH in deficiency states—a combination of these two techniques is required to maximize physiologic information. This combination of approaches is especially appealing as each line of investigation by itself offers a unique insight into a different aspect of GnRH physiology, but at the same time suffers from a major potential limitation.

Regulation of luteal function in domestic ruminants: new concepts.

Abstract: Publisher Summary This chapter discusses the control of luteal function in domestic ruminant animals. It focuses on data regarding the regulation of receptors for luteinizing hormone (LH) and the characterization of two distinct types of steroidogenic luteal cells. The function of the corpus luteum in ruminants is regulated by a complex interaction of the secretions from at least two other endocrine organs. The adenohypophysis secretes LH, generally accepted as the primary luteotropic hormone in these species. The chapter suggests that the number of luteal receptors for LH—but not circulating concentrations of LH—is correlated with serum levels of progesterone throughout the estrous cycle of ewes. Down-regulation of LH receptors depends upon occupancy of the receptor, based on correlation between number of receptors occupied and number lost after administration of 1 mg of LH in vivo. The major pathway for loss of human chorionic gonadotropin (hCG) or LH bound to the luteal receptor for LH is via internalization and degradation of the hormone. Over 80% of 125I-labeled hCG bound to luteal cells in culture is internalized and degraded. A lesser amount of 125I-labeled LH is internalized and degraded because more of this hormone dissociates from the receptor. A major portion of the internalized population of receptors is recycled to the plasma membrane.

Neurohormones from fish tails: the caudal neurosecretory system. I. "Urophysiology" and the caudal neurosecretory system of fishes.

Abstract: Publisher Summary This chapter discusses the urophysiology and the caudal neurosecretory system of fishes, chemistry of urotensin II, immunocytochemistry of the caudal neurosecretory system, biological activities of urotensin II in teleosts, and effects of urotensin II in mammals. The caudal system in teleosts is heavily innervated, consistently by aminergic input and occasionally by cholinergic and peptidergic pathways from the brain. The complexity and intensity of the innervation shows some important physiological role for this system; yet, it has been difficult to ascribe a definite functional contribution to the caudal system and its hormones—the urotensins. The urophysis contains and presumably releases a variety of substances: (1) urotensin I—a 41-amino acid peptide which is homologous and analogous to mammalian corticotropin-releasing factors (CRFs); (2) urotensin II—a 12-amino acid peptide which is partially homologous and partially analogous to somatostatin-14; (3) urotensin IV—indistinguishable from arginine vasotocin and present in only a few teleost species; (4) urophysins—putative carrier proteins, cysteine-free, analogous to the neurophysins and with unknown biogenetic relationships to the urotensins; and (5) acetylcholine—the highest concentrations of this substance reported for any tissue but of unknown significance in this locale.

Regulation of hormone receptors and adenylyl cyclases by guanine nucleotide binding N proteins.

Abstract: Publisher Summary Receptors that affect cyclic adenosine monophosphate (cAMP) are sub-classified into two subtypes: Rs receptors, which increase cAMP levels by stimulating the enzyme adenylyl cyclase, and Ri receptors, which decrease cAMP levels by inhibiting the cAMP-forming enzyme. This chapter discusses the transduction mechanism to which Rs- and Ri-type receptors couple to modulate adenylyl cyclase activity. At the center of this transduction mechanism are two oligomeric coupling proteins called N or G proteins. These proteins have properties to bind and hydrolyze guanosine triphosphate and regulate hormone affinity for receptors and the catalytic activity of the cAMP-forming enzyme. This complex receptor-coupling protein-adenylyl cyclase system is approached by first reviewing structural and functional aspects that regulate cAMP formation. The chapter also discusses the basic structure and regulation of adenylyl cyclase by nucleotides and magnesium. It also discusses action of hormones on the nucleotide-regulated system. It analyzes the known regulation of hormone-receptor interaction by the coupling proteins. The analysis of affinity regulation of receptors leads to conclusions that point toward the existence of at least two conformational states of receptors interacting with at least three conformational states or forms of the coupling proteins.

Progestin action and progesterone receptor structure in human breast cancer: a review.

Abstract: Publisher Summary This chapter discusses the current information about progestin action, and progesterone receptors (PR) structure and function It presents a recent study in which a progestin-responsive human breast cancer cell line has been used to study the biochemical mechanisms involved in progesterone action Progesterone is essential for human breast alveolar gland development and growth It is not only a mitogenic hormone but also acts in synergy with estradiol to prime the mammary gland to respond to mitogens like prolactin, glucocorticoids, and growth hormone At puberty, estradiol induces mammary duct formation As the hypothalamic-pituitary-ovarian axis matures, there is a brief phase of anovulatory cycles during which the mammary gland is influenced principally by estrogens Once ovulation is established, corpus luteum produces progesterone, which stimulates growth of the lobuloalveolar structures During the reproductive years, progesterone promotes differentiation of alveolar cells into secretory cells, and dilation of the duct system In conjunction with prolactin and other metabolic hormones, progesterone stimulates lipid droplet formation, and secretory activity While prolactin and growth hormone are the most important pituitary hormones affecting growth of the mammary gland during pregnancy, it is estradiol and progesterone that prevent the full expression of their secretory effects on the mammary epithelium At parturition, the sudden withdrawal of these two hormones permits the breast to respond to the lactogenic hormones

Hypothalamic pulse generators.

Abstract: Publisher Summary This chapter describes pulsatile hormone secretion and analyzes the mechanisms underlying the neural organization of this phenomenon in context of oxytocin and luteinizing hormone releasing hormone (LHRH) secretion. It also discusses five concepts— (1) oxytocin and LHRH are both released from the hypothalamus in pulses superimposed upon a continuous or intermittent low level of secretion; these two modes of secretion can produce separate actions, or one might govern the response to the other; (2) the synchronous generation of action potentials at a very fast rate within a population of peptidergic neurones provides the neural substrate for the release of a hormone pulse; (3) the control of interpulse interval is determined by events within the brain, though the interval generator may not reside within the neurons that secrete oxytocin or LHRH; (4) amplitude modulation of pulsatile secretion can relate to different levels of electrical activation within the brain and/or to differences in the responsiveness of the target tissues that transduce the pulsatile signal; and (5) opioid peptides inhibit the secretion of both oxytocin and LHRH. This involves an inhibition of stimulus-secretion coupling within the nerve terminals, and possibly an inhibition of synaptically mediated events that impinge upon the cell bodies of the peptidergic neurons within the hypothalamus.

Progesterone action on the LHRH and the nigrostriatal dopamine neuronal systems: in vitro and in vivo studies.

Abstract: Publisher Summary This chapter presents the in vitro and in vivo progesterone action on the luteinizing hormone releasing hormone (LHRH) and the nigrostriatal dopamine neuronal systems (NS-DA). The effect of progesterone (P4) on neuroendocrine reproductive functions can be characterized by a two-phase process, initially an activational phase followed several hours later by an inhibitory phase. The chapter focuses on this biphasic, stimulatory-inhibitory effect of P4. It discusses some descriptive data on the action of P4 on the NS-DA system of rats. This system is a typical closed neuronal circuit involving cell bodies clustered in the zona compacta of the substantia nigra with long dopamine axons terminating in the corpus striatum. The chapter also discusses the action of P4 on the LHRH neuronal system, a system which includes two anatomically distinct clusters of cell bodies—one in the preoptic-septum area and the other in the mediobasal hypothalamus. This classic neuroendocrine circuit is an open-loop system whose major output at the level of the median eminence, the 10 amino acid decapeptide LHRH, controls the release of LH and reproductive functions.

Trophic stimulation of steroidogenesis: in search of the elusive trigger.

Abstract: Publisher Summary This chapter describes trophic stimulation of steroidogenesis. It discusses the source of mitochondrial cholesterol and mechanism of cholesterol transport. The fact that the side-chain cleavage system is confined to mitochondria made the source of energy for side-chain cleavage a subject of considerable interest. It has been found that in beef adrenal, the side-chain cleavage reaction can use reversed electron transport and transhydrogenation as a source of reducing equivalents in the form of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) for the cleavage reaction. Mitochondrial malic enzyme—suggested as a NADPH source for 11β-hydroxylation—cannot account for the greater consumption of NADPH required for side-chain cleavage. This information does not reveal how adrenocorticotropic hormone (ACTH) regulates the rate of production of pregnenolone. There is no evidence that suggests that ACTH or cyclic adenosine monophosphate increases the NADPH production by adrenal. Purification of the side-chain cleavage enzyme from beef adrenal reveals important properties of the enzyme, such as the stoichiometry of the reaction, the involvement of heme in the cleavage of 20,22 bond, and aggregation of the enzyme to an active form composed of 16 subunits. However the mechanism of action of ACTH is still unknown.

The Defective Glucocorticoid Receptor in Man and Nonhuman Primates

Abstract: Publisher Summary This chapter reviews the examples of end-organ resistance to cortisol in primates and discusses the pathophysiologic and evolutionary mechanisms involved, and their implications for the structure of receptors. It focuses on the following steroid hormone-receptor systems that appear to be altered in New World primates in the form of end-organ resistance: (1) glucocorticoid resistance, associated with high free plasma cortisol concentrations and low affinity glucocorticoid receptors, (2) aldosterone resistance, associated with high plasma aldosterone and low renal aldosterone receptor concentrations also characterized by diminished cross-reactivity for cortisol, (3) progesterone resistance, characterized by high levels of plasma progesterone and low concentrations of uterine cytosol progesterone receptors, (4) estrogen resistance, characterized by high levels of estradiol in plasma and low uterine cytosol estrogen receptors, (5) androgen resistance characterized by high free plasma testosterone concentrations and possible changes of the androgen receptors, and associated with low 5 α -reductase activity at the target tissues, and (6) vitamin D resistance characterized by high levels of 1,25-dihydroxy vitamin D and low concentrations of intestinal vitamin D receptors. As it is difficult to hypothesize a random simultaneous occurrence of six different mutations affecting all six steroid hormone-receptor-acceptor systems, it is believed that it is possible that the concurrent alterations of the glucocorticoid, mineralocorticoid, sex steroid, and vitamin D receptor systems reflect some fundamental change in the chromatin proteins or DNA sequences involved in steroidal regulation of gene transcription, putatively common to the different steroid hormones.

Neurohormones from fish tails. II: Actions of urotensin I in mammals and fishes.

Abstract: Publisher Summary This chapter discusses the actions of urotensin I (UI) in mammals and fishes The vascular actions of UI are investigated in several mammalian species in order to isolate UI in a highly purified form and to determine its structure in two teleosteans In the conscious or the urethane anesthetized rat, UI induces a marked, dose dependent, and a long lasting hypotensive effect—20 minutes to 6 hours in duration after intravenous administration and in excess of 24 hours after subcutaneous administration in spontaneously hypertensive rats An investigation of the hypotensive vasodilatory actions in different vascular regions reveals that in the rat, vasodilatation is most pronounced in the gastrointestinal region but it can be observed in most major vascular beds In vitro, the rat mesenteric artery is the most sensitive preparation In the rat, the distribution of UI specific binding sites can be determined in various major blood vessels, mainly arteries Specific binding is also seen in the liver and kidney In contrast to the rat, significant high-capacity, high-affinity binding sites in the dog are only found in the mesenteric artery Two classes of binding sites are present in the dog artery, unlike the rat mesenteric artery

Thyrotropin-releasing hormone action: mechanism of calcium-mediated stimulation of prolactin secretion.

Abstract: An elevation of cytoplasmic free calcium ion concentration ([Ca 2+ ] i ) 1 serves to couple the interaction of many hormones and neurotransmitters with plasma membrane receptors to the stimulation of a variety of cellular processes. This chapter discusses the intracellular events that couple thyrotropin-releasing hormone (TRH)-receptor interaction to the elevation of [Ca 2+ ] I in GH 3 cells. In order to understand the molecular mechanisms that mediate the elevation of [Ca 2+ ] i , it is important to identify both the potential mediators of this effect and the pool of calcium that contribute to the increase in [Ca 2+ ] i . For the investigations, GH 3 cells are utilized, a cloned cell line that is widely employed as a model to study the physiology of pituitary mammotropic cells. The chapter presents evidence from the studies in GH 3 cells—(1) TRH stimulates an elevation of [Ca 2+ ] i in part by mobilizing calcium from an intracellular, nonmitochondrial pool; (2) TRH stimulates the rapid, phospholipase C-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2 ), a minor plasma membrane phospholipid, to yield inositol 1,4,5-trisphosphate (InsP 3 ); (3) InsP 3 is capable of rapidly mobilizing calcium from an intracellular, non mitochondrial pool. Based on these observations, the chapter explains that TRH stimulates the hydrolysis of PtdIns(4,5)P 2 to InsP 3 that, in turn, mobilizes calcium from a nonmitochondrial pool leading to elevation of [Ca 2+ ] i then to activation of exocytosis and to stimulated prolactin secretion.

Glycosylation and Posttranslational Processing of Thyroid-Stimulating Hormone: Clinical Implications

Abstract: Publisher Summary This chapter discusses clinical implications of glycosylation and posttranslational processing of thyroid-stimulating hormone (TSH). TSH is a glycoprotein hormone of molecular weight 28,000 which is composed of two noncovalently linked subunits, α and β . It is chemically related to the pituitary gonadotropins, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and to chorionic gonadotropin (CG). Elevated serum α /TSH ratios have been described in patients with TSH-secreting pituitary tumors. The excess production from such tumors has been of value in differentiating patients with neoplastic from non-neoplastic causes of TSH-induced hyperthyroidism. In addition, isolated production of α subunit, without concomitant production of TSH or gonadotropins, by certain pituitary adenomas and other malignant tumors is demonstrated. Elevated serum TSH- β /TSH ratios are described in two patients, one with an enlarged thyroid and one with an enlarged pituitary. The TSH- β in both cases have large molecular weight, display immunologic properties different from standard TSH- β , and is unresponsive to thyrotropin releasing hormone. Although this unusual form of TSH- β has been partially characterized, its significance remains unknown. The chapter also describes unusual forms of human TSH with decreased bioactivity. One apparently normal subject was found to have a high-molecular-weight form of TSH with normal receptor-binding properties but decreased bioactivity. Such forms can result from aggregated or protein-bound TSH caused by abnormalities of glycosylation, similar to those noted after tunicamycin treatment.

Regulation of microsomal cytochrome P-450 enzymes and testosterone production in Leydig cells.

Abstract: Publisher Summary This chapter describes the studies that examine the mechanisms by which luteinizing hormone (LH) or cyclic adenosine monophosphate (cAMP) desensitize steroidogenic response on one hand, but cause an increase in steroidogenic capacity in the same cell type under other conditions. It focuses on the effects of LH or cAMP on the degradation and synthesis of the microsomal P-450 enzymes, 17α-hydroxylase and C17–20lyase, and the relationship of changes in these activities to changes in steroidogenic capacity. The chapter provides an overview on new insights into the mechanism by which the microsomal cytochrome P-450 enzymes, 17α-hydroxylase, and C17–20lyase of Leydig cells are maintained at a constant level under normal physiological conditions. Pulsatile stimulation of Leydig cells by LH in vivo increases cAMP levels—by some yet unknown mechanism—that increases synthesis of the microsomal P-450 enzymes. In addition, cAMP increases steroid hormone production by increasing the availability of the precursor, cholesterol, for further metabolism to testosterone. The steroid products, present at elevated concentrations, can act as pseudo substrates for P-450 enzyme, and in the presence of oxygen, a P-450-pseudosubstrate-O2 complex is formed.

Creation of transgenic animals to study development and as models for human disease.

Abstract: Publisher Summary The mechanism of cells to regulate gene expression is a question of great importance in modern biology because the unique features of each cell and ultimately complex tissues are by and large determined by their unique patterns of gene expression. This chapter discusses the genetic basis of development and differentiation by transforming entire mammalian organisms. The technique is to inject the foreign gene into a very early mouse embryo and then return the embryo to a foster mother mouse to complete its development. The data strongly suggests that the altered phenotype of the mice is a direct result of the integration and expression of the metallothionein-growth hormone fusion gene. The elevated level of growth hormone (GH) present in some of these mice corresponds to a high level of MGH messenger RNA (mRNA) in the liver. The high level of MGH gene expression in transgenic mice greatly facilitates direct comparison of MGH and MT-I mRNA production in different tissues, thus determining whether chromosomal location has an important effect on tissue-specific expression of the MT-I promoter. GH levels in some of the transgenic mice are as much as 800-fold higher than in normal mice, resulting in animals nearly twice the weight of their unaffected littermates. This greater than normal accumulation of GH reflects both the lack of normal feedback mechanisms and expression of this gene in many large organs including liver, kidney, and intestine.

Neuropeptides: interactions and diversities.

Abstract: Publisher Summary This chapter describes the interactions between the transmitters of convergent synaptic inputs on their presumed common target cells. In particular, interactions between norepinephrine—the transmitter of the globally directed coeruleo-cortical projection, and vasoactive intestinal polypeptide (VIP)—one of the peptides attributed to the intrinsic local interneurons of the rodent cerebral cortex, the bipolar neurons has been studied. In a similar manner, interactions in hippocampus between somatostatin—a peptide found within several neuronal elements of the limbic system, and acetylcholine—long presumptive transmitter for the septohippocampal pathway, is also studied. The chapter also discusses the use of molecular genetics approaches to define those neuropeptides, which are yet to be discovered. It discusses a strategy to discover brain specific molecules. It also discusses some early findings with this strategy to exemplify some potentially important new directions in the quest to completely unravel the chemical and functional organization of the nervous system.