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Biomedical subjects

K J Catt

Publications and source records attributed to K J Catt.

At least 325 records · Page 18Linked to original sources
PubMed1981

Gonadotropin-releasing hormone: regulation of adenosine 3',5'-monophosphate in ovarian granulosa cells.

The antigonadal effects of gonadotropin-releasing hormone in ovarian granulosa cells are due to attenuation of the adenosine 3',5'-monophosphate (cyclic AMP) response to follicle-stimulating hormone. Agonists of gonadotropin-releasing hormone progressively inhibit adenylate cyclase and stimulate phosphodiesterase activities in cultured granulosa cells, indicating that blockade of gonadotropin action is attributable to the combined effects of decreased production and increased degradation of cyclic AMP.

Animals↗
PubMed1981

Somatostatin modulates effects of angiotensin II in adrenal glomerulosa zone.

The octapeptide angiotensin II is a major regulator of the adrenal glomerulosa zone, acting both as an acute stimulus of aldosterone secretion and as a trophic hormone which increases steroidogenic enzymes and angiotensin II receptors in glomerulosa cells. Angiotensin II also mediates the adrenal effects of altered sodium balance, and is essential for the aldosterone response to sodium restriction. However, the adrenal effects of angiotensin II are attenuated during sodium loading, suggesting that other local or humoral factors modulate its actions on adrenal glomerulosa function. Somatostatin, the somatotropin release inhibiting factor of the hypothalamus, has been shown to inhibit the secretion and action of several pituitary and non-pituitary hormones. Because somatostatin has been found in several non-neural tissues, and seems to act as a local regulator of endocrine function, we have now examined the possibility that it may also modulate the effects of angiotensin II in the adrenal glomerulosa cell. Our studies have shown that low concentrations of somatostatin specificity inhibit the production of angiotensin II-stimulated aldosterone, and that this action is mediated by specific, high-affinity receptors for somatostatin in the zona glomerulosa.

Adrenal Glands↗
PubMed1981

Interaction of fluorescent gonadotropin-releasing hormone with receptors in cultured pituitary cells.

A fluorescent derivative of the gonadotropin-releasing hormone (GnRH) agonist analog, [D-Lys6]GnRH, was synthesized for receptor studies and shown to be biologically active. The rhodamine-derivatized peptide (Rh-GnRH) retained 40% of the receptor binding activity of [D-Lys6]GnRH, and 50% of the luteinizing hormone-releasing activity assayed in cultured pituitary cells. The fluorescent analog was employed to visualize the distribution of GnRH receptors in cultured pituitary cells, using the technique of video-intensified fluorescence microscopy. The binding of Rh-GnRH was confined to the large gonadotrophs which comprised 15% of the cell population. The specificity of the binding was shown by the absence of significant fluorescence in the presence of a 100-fold excess of [D-Lys6]GnRH, or when Rh-GnRH was incubated with choriocarcinoma, neuroblastoma, or 3T3 cell lines devoid of GnRH receptors. The interaction of Rh-GnRH with living pituitary cells was characterized by an initial diffuse distribution, followed by the formation of polar aggregates that later appeared to be internalized. These observations emphasize the value of fluorescent derivatives of GnRH for elucidating the course of the interaction with specific receptors on pituitary gonadotrophs. The initial results indicate that GnRH-receptor complexes undergo aggregation during stimulation of luteinizing hormone release, and are later internalized for subsequent degradation and/ or intracellular actions.

Animals↗
PubMed1981

Mechanism of action of gonadotropin-releasing hormone. Involvement of phospholipid turnover in luteinizing hormone release.

The action of gonadotropin-releasing hormone (GnRH) upon luteinizing hormone (LH) secretion is calcium-dependent, but is not mediated by cyclic AMP, cyclic GMP, or prostaglandins. The role of calcium-mediated phospholipid turnover in GnRH action was investigated in 2-day cultured pituitary cells, in which the production and target cell effects of arachidonic acid were analyzed in relation to GnRH-stimulated LH release. Addition of 10(-8) M GnRH, which stimulated LH release 5-fold, caused a 35% increase in the rate of [3H]arachidonic acid release from prelabeled phospholipids. The effects of GnRH on arachidonic acid and LH release, which occurred within 10 min, were calcium-dependent and were not accompanied by a change in [3H]prostaglandin formation. The phospholipase A2 inhibitors, chloroquine and quinacrine, prevented the effect of GnRH on arachidonic acid formation and LH release. Addition of exogenous arachidonic acid or phorbol myristate acetate (which increases endogenous arachidonic acid) caused a dose-related release of LH, whereas prostaglandin E2 had no effect. Although GnRH action was highly calcium-dependent, stimulation of LH release by arachidonic acid was unaltered in the absence of extracellular calcium. The effect of arachidonic acid on LH release did not depend on conversion to prostaglandins and was not additive with the action of a maximal stimulating concentration of GnRH. These results demonstrate that GnRH increases arachidonic acid formation from the phospholipids of pituitary gonadotrophs, and indicate that the fatty acid or its metabolites can initiate LH release.

Animals↗
PubMed1981

Circulating angiotensin II and adrenal receptors after nephrectomy.

Mineralocorticoid secretion is predominantly controlled by the octapeptide angiotensin II, which exerts trophic actions on the adrenal glomerulosa and acute regulatory effects on aldosterone biosynthesis. The trophic actions include stimulation of angiotensin II receptors and enzymes of the aldosterone biosynthetic pathway, with corresponding enhancement of the aldosterone secretory capacity of the adrenal gland. The positive regulatory action of angiotensin II on its adrenal receptors occurs with elevations of the circulating peptide concentration within the physiological range and probably contributes to the increased sensitivity of the adrenal during sodium deficiency. In this action, angiotensin II differs from other hormones which decrease their target-cell receptors. However, the increase in adrenal angiotensin II receptors following nephrectomy has been interpreted as evidence for a tonic down-regulating effect of angiotensin II on its adrenal receptors. To clarify these conflicting views we evaluated the effects of nephrectomy on adrenal angiotensin II receptors in relation to blood angiotensin II and plasma electrolyte levels. We show here that hyperkalaemia contributes markedly to the post-nephrectomy increase in adrenal angiotensin II receptors, and that circulating angiotensin II levels persist for an unexpectedly long period after nephrectomy, presumably due to tissue generation of the octapeptide.

Adrenal Cortex↗
PubMed1981

Gonadotropin-releasing hormone inhibits cyclic nucleotide accumulation in cultured rat granulosa cells.

Ovarian granulosa cells obtained from hypophysectomized, diethylstilbestrol-treated rats were cultured in the presence of ovine follicle-stimulating hormone (FSH) and gonadotropin-releasing hormone (GnRH). FSH stimulated the production and accumulation of both cAMP and cGMP, as well as progesterone, during a 48-h incubation period. Addition of GnRH or an agonist analog, [D-Ala6]des-Gly10-GnRH N-ethylamide (GnRHa), did not influence the cyclic nucleotide response to FSH in the first 6 h of incubation, but caused dose-dependent inhibition of the FSH-induced rise in cyclic nucleotide production from 24 to 48 h of incubation. Cellular production of both cyclic nucleotides and progesterone was decreased by GnRHa concentrations as low as 10(-12) M, with maximum inhibition at 10(-9) M GnRHa. These results suggest that the in vitro antigonadal actions of GnRH and related peptides are expressed through inhibition of cyclic nucleotide production.

Animals↗
PubMed1981

Hormonal regulation of cytodifferentiation and intercellular communication in cultured granulosa cells.

Granulosa cells from immature hypophysectomized diethylstilbestrol-treated rats displayed pronounced intracellular and intercellular changes after 48 hr of exposure to follicle-stimulating hormone (FSH) in vitro. As determined by light and electron microscopy, most of the FSH-treated cells became highly aggregated and grew in multilayered clusters. Numerous gap junctions were seen between cells, indicating the presence of significant intercellular communication. Microvilli densely covered the surface of the hormone-stimulated cells, which contained enlarged mitochondria with convoluted cristae, characteristic of steroidogenic cells. Luteinizing hormone receptors, identified by autoradiography with 125I-labeled human chorionic gonadotropin, were mainly associated with aggregated cells, whereas single cells were usually free of the labeled hormone. Addition of a gonadotropin-releasing hormone agonist prevented the appearance of luteinizing hormone receptors and markedly impaired cyclic AMP and progesterone production, as well as the morphological changes induced by FSH. The majority of the granulosa cells grown in the absence of either hormone assumed a flattened, and smooth shape and grew primarily in monolayers. The maintenance of cellular aggregation and intercellular communication by FSH, and its inhibition by gonadotropin-releasing hormone, may play an important role in the cytodifferentiation of ovarian granulosa cells.

Animals↗
PubMed1981

Mechanisms of inhibition of aldosterone secretion by adrenocorticotropin.

The mechanisms by which prolonged administration of ACTH causes a decrease in aldosterone secretion were studied in the rat. After 6 days of treatment with ACTH (2 U/day), blood corticosterone was elevated and plasma aldosterone was decreased in rats maintained on either a normal or low sodium diet. PRA was also decreased, probably secondary to increased sodium and/or fluid retention. In collagenase-dispersed glomerulosa cells from adrenals of ACTH-treated rats, angiotensin II receptors were markedly decreased, as were the in vitro aldosterone responses to angiotensin II, ACTH, 8-bromo-cAMP, and potassium. However, the production of deoxycorticosterone and precursor steroids was increased, indicating the presence of a block in the late aldosterone biosynthetic pathway. Measurement of the activity of biosynthetic enzymes of the steroidogenic pathway in isolated mitochondria revealed an 80% increase in side-chain cleavage enzyme in both glomerulosa and fasciculata mitochondria from ACTH-treated rats. Although ACTH injection also increased 11-hydroxylase activity in the fasciculata zone, this enzyme was reduced by 50% in capsular mitochondria. The 18-hydroxylase activity in adrenal capsular mitochondria was markedly decreased by ACTH treatment in both normal and sodium-restricted animals. The importance of ACTH-induced steroidogenesis in the development of altered glomerulosa cell function was indicated by the ability of aminoglutethimide to prevent the inhibitory effects of ACTH on angiotensin II receptors and PRA. It is likely that the observed inhibition of the renin-angiotensin system is responsible for the decrease in angiotensin II receptors and 18-hydroxylase, since both are highly dependent on the trophic effect of angiotensin II. The specific lesions produced in adrenal glomerulosa cells by long term ACTH treatment include decreased levels of angiotensin II receptors, 11-hydroxylase, and 18-hydroxylase. These changes are secondary to the suppression of renin-angiotensin activity and are responsible for the impaired aldosterone secretion that results from prolonged treatment with ACTH. (Endocrinology 108: 522, 1981)

Adrenal Glands↗