ISSN:1663-2818    

DOI:10.1159/000181076

出版商:S. Karger AG    

年代:1989

数据来源: Karger

ISSN:1663-2818    

DOI:10.1159/000181077

出版商:S. Karger AG    

年代:1989

数据来源: Karger

ISSN:1663-2818    

DOI:10.1159/000181078

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The concept of multifactorial pituitary control is now well established. As in other cell systems, integration of complex messages involves dynamic interactions of receptors and coupling mechanisms. Regulation of adenohypophyseal secretions has been shown to involve cyclic AMP production, the modulation of phosphatidylinositol phosphate breakdown and Ca2+ mobilization. Dopamine, somatostatin and angiotensin II receptors are negatively coupled to adenylate cyclase in anterior pituitary cells. In the case of angiotensin, this effect on adenylate cyclase appears paradoxical since the peptide markedly stimulates prolactin secretion. In fact, angiotensin II also markedly stimulates inositol phosphate production and this effect could account for the stimulated hormone secretion. In addition, dopamine could inhibit inositol phosphate production stimulated by angiotensin II and thyrotropin-releasing hormone. Dopamine and somatostatin also directly modulate voltage-dependent calcium channels, perhaps through a direct coupling with potassium channels. On the other hand, steroids modulate the sensitivity of adenohypophyseal cells to neurohormones by different mechanisms. In the case of somatostatin, it increases the number of specific binding sites, while in the case of dopamine estradiol affects the transduction mechanisms of D2 dopamine receptors. In conclusion, dopamine and somatostatin receptors appear coupled to various transduction mechanisms through pertussis-sensitive G proteins in anterior pituitary cells.

ISSN:1663-2818    

DOI:10.1159/000181079

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

In order to go further into the pathogenesis of human pituitary adenomas, we studied receptors for neurohormones (thyroliberin, TRH; dopamine, DA; somatostatin, SRIH), for estradiol and epidermal growth factor (EGF) thought to influence hormone secretion and/or cell growth. The following results were obtained: (1) the receptors listed above, with the exception of EGF receptors in the adenomas, are present in normal pituitary tissue and in prolactin (PRL)- and growth hormone (GH)-secreting adenomas; (2) they are functional and their affinities are not different in normal or tumoral tissues; (3) their density is variable and depends on the type of secreting adenoma (GH or PRL), the size of the tumor and the plasma level of the hormone which is secreted, and (4) in nonsecreting adenomas, only TRH receptors are found with characteristics identical to those observed in secreting adenomas. We also showed that TRH is contained in normal and tumoral pituitary tissues. TRH and SRIH are released in vitro from adenomatous cells in large amounts, suggesting their possible synthesis by the pituitary. In both cases a local regulation is observed. TRH release is stimulated in the presence of DA while SRIH is inhibited in the presence of TRH. This neuropeptide release may be implicated in the pituitary hormone regulation through a paracrine or an autocrine mechanism. Thus, the neurohormone receptors found in pituitary adenomas should be dependent on a more complex regulation than it has been envisaged till now.

ISSN:1663-2818    

DOI:10.1159/000181080

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

In most of human prolactin (PRL)-secreting adenomas, dopamine and dopamine agonists normally suppress the excessive PRL secretion. Nevertheless, a subpopulation of such patients presents a relative insensitivity to the ergot derivative bromocriptine. Six patients with a macroadenoma (n = 5) or microadenoma (n = 1) were considered resistant to bromocriptine which, at a daily dose of 15–60 mg, did not normalize high plasma PRL levels. Culture studies of these adenoma cells showed that: (1) 10–8M bromocriptine produced a 32 ± 16% inhibition of PRLrelease versus 65 ± 12% obtained in the same conditions with normal human pituitary cells; (2) sulpiride (10–6M) reversed the inhibitory effects of bromocriptine, and (3) the bacterial endotoxins, cholera toxin (l0–11M) and pertussis toxin (250 ng/ml), respectively, produced a 45–500% increase and a total abolition of bromocriptine induced PRLinhibition. These observations and recent data of the literature allow to discuss the possibility of receptor or postreceptor defects in

ISSN:1663-2818    

DOI:10.1159/000181081

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Angiotensin II (All) is present in gonadotropes in rats, and there are All receptors on lactotropes and corticotropes. All may be a paracrine mediator that stimulates the secretion of prolactin and adrenocorticotropin (ACTH) at the level of the pituitary, but additional research is needed to define its exact role. Angiotensinogen may also reach the gonadotropes via a paracrine route. On the other hand, there is considerable evidence that brain All stimulates the secretion of luteinizing hormone (LH) by increasing the secretion of LH-releasing hormone, and that this effect is due to All-mediated release of norepinephrine from noradrenergic nerve terminals in the preoptic region of the hypothalamus. In addition, brain All inhibits the secretion of prolactin, probably by increasing the release of dopamine into the portal hypophyseal vessels. Circulating All stimulates the secretion of a third anterior pituitary hormone, ACTH, by acting on one or more of the circumventricular organs to increase the secretion of corticotropin-releasing hormone.

ISSN:1663-2818    

DOI:10.1159/000181082

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Aging is characterized by changes in neuroendocrine/endocrine functions which are manifest in female reproductive physiology and less perceptible in other functions such as thyroid, adrenal or growth/metabolic functions. The contribution of each level of the axis – hypothalamus, adenohypophysis or peripheral tissues – is not clearly established. Functional impairments with age are recognized in the peripheral glands (gonad, thyroid, adrenal) as well as in the pituitary, but increasing evidence is accumulating for a marked contribution of the hypothalamus in the age-associated endocrine changes observed in animals and humans. In old rats, multineuronal dysfunctions are demonstrated in the hypothalamus, with a documented decline in the activity of the neurons producing dopamine and thyrotropin-releasing hormone, and to a lesser extent luteinizing hormone- and growth hormone-releasing hormones, and alterations in regulatory mechanisms of these neurons are disclosed. Moreover, impairments are observed in the processing – binding, accumulation and intracellular distribution – of hypothalamic hormones in the adenohypophysis of old rats. Taken together, these observations are supportive of the view that the neuroendocrine/endocrine changes appearing with age result from a complex balance of functional alterations occurring at each level – central and peripheral –

ISSN:1663-2818    

DOI:10.1159/000181083

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Changes in female reproductive function occur relatively early during the life span in many mammalian species. Therefore, this physiological system is an excellent model system in which to study the effects of age on specific endocrine relationships since changes occur prior to the occurrence of multiple pathologies associated with later stages of aging. Data from several laboratories suggest that changes in hypothalamic, pituitary and ovarian function may contribute to age-related deterioration of fertility in females. We will focus our attention on the role of hypothalamic changes in the cascade of events that eventually lead to acyclicity and infertility. Data suggest that changes in the diurnal rhythmicity of catecholaminergic neurotransmitters and their receptors occur during middle age. These changes may regulate the pattern of release of GnRH since alterations in the pulsatile pattern of LH secretion also become detectable at this age. Some age-related changes in hypothalamic and pituitary function are not irreversible or absolutely determined. Instead it appears that the ovarian steroidal milieu modulates the rate of aging of several aspects of hypothalamohypophysial function. In summary, changes in hypothalamic and pituitary function appear to contribute to the aging of the female reproductive system.

ISSN:1663-2818    

DOI:10.1159/000181084

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Somatostatin (SRIF) actions in the brain and pituitary are mediated by specific receptors. Using radioiodinated ligands it has been possible to characterize the kinetics of specific binding sites in the brain and pituitary, and to determine their cellular localization by autoradiography. At the pituitary level, the inhibition of growth hormone, prolactin and thyrotropin secretions induced by SRIF is mediated through a single binding site which is coupled to the inhibition of adenylate cyclase. In the brain, SRIF receptors are localized on neurons and glial cells and are also coupled to adenylate cyclase inhibition. Two sites are differentiated in the brain with an analogue of somatostatin, SMS 201995. In humans, SRIF-binding sites have been related to a number of pathologies. At the pituitary level, it has been shown that the number of binding sites was negatively correlated to growth hormone levels in acromegaly. Furthermore, SRIF-binding sites were undetectable in a patient which did not respond to SMS 201995 therapy. In the brain, meningiomas and gliomas are rich in SRIF binding sites. This suggests a possible role for SRIF on glia. In neuro-degenerative diseases, cortical SRIF concentrations are decreased in Alzheimer’s and Parkinson’s disease associated with dementia while SRIF-binding sites are only affected in Alzheimer’s disease. In conclusion, the physiological role of SRIF in the brain and pituitary can be evaluated by studying the receptors of the peptide. Such studies allow to question the implication of SRIF in endocrine and neuropathol

ISSN:1663-2818    

DOI:10.1159/000181085

出版商:S. Karger AG    

年代:1989

数据来源: Karger