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K J Catt

Publications and source records attributed to K J Catt.

At least 361 records · Page 20Linked to original sources
PubMed1980

Regulation of pituitary receptors for gonadotropin-releasing hormone during the rat estrous cycle.

A radioiodinated superagonist analog of gonadotropin-releasing hormone (GnRH:[D-Ser(TBu)6]des-GLy10-GnRH N-ethylamide) was used to quantitate the GnRH receptor content of single pituitary glands. This ligand binds with high affinity (Ka = 4.9 X 10(9) M-1) to a single class of sites in pituitary homogenates, without significant tracer degradation, during equilibration for 80 min at 4 C. The GnRH receptor content of adult male rat pituitaries [112 +/- 6.4 (SE) fmol/gland; n = 9] was similar to that of adult female rat pituitaries obtained at estrus or metestrus (104.8 +/- 6.4 fmol/gland, n = 13). Between 1800 h on metestrus and 1800 h on diestrus, the pituitary content of GnRH receptors increased to 200 fmol/gland or greater in each of three separate experiments. The pituitary content of GnRH receptors remained elevated until the time of the serum LH surge, then consistently fell sharply to metesterus levels. These data imply a physiological relevance for the GgRH-binding sites measured by radioassay and demonstrate their relationship to the events of the estrous cycle. The increased GnRH receptor content from the evening of diestrus until late in the afternoon of proestrus may contribute to the enhanced sensitivity of the pituitary to GnRH during proestrus. The close temporal relationship between rising blood estrogen levels and increasing pituitary GnRH receptors suggests that steroid-mediated receptor induction occurs before proestrus. Such an effect of estrogen could be exerted directly upon the pituitary gland or indirectly via the hypothalamus to increase the release of endogenous GnRH, which subsequently induces its own receptors in pituitary gonadotrophs.

Animals↗
PubMed1980

Characterization of gonadotropin-releasing hormone receptors in cultured rat pituitary cells.

The properties of gonadotropin-releasing hormone (GnRH) receptors were analyzed in isolated pituitary cells prepared by enzymatic dispersion with trypsin or collagenase-hyaluronidase. The initial impairment of LH responses to GnRH in isolated cells prepared by both methods was reversed during culture for 2 days in multiwell vessels. However, specific binding sites for GnRH, assayed by equilibration with [125I]iodi0[D-Ser(t-BU)6]des-Gly10-GnRH N-ethylamide (GnRH-A) were demonstrable in collagenase-dispersed cells, both initially and after 2 days in culture. Cellular uptake of GnRH-A was temperature dependent, with rapid and saturable binding to a limited number of specific receptor sites with high affinity for the labeled analog (Ka = 4.0 +/- 0.8 X 10(9) M-1). These sites showed common binding specificity for GnRH-A and the native GnRH peptide, with significantly lower affinity for the natural peptide (Ka = 2.3 X 10(7) M-1). Other protein and peptide hormones, including ovine LH, ovine PRL, hCG, TRH, somatostatin, and angiotensin II (up to 10(-6) M) did not inhibit binding of GnRH-A to its receptors. Cellular binding of GnRH-A was followed by increased cGMP production and LH release within 10 min. The analog was 50 times more potent than native GnRH in stimulating LH release. The Kact values derived for GnRH and GnRH-A were 0.5 and 0.01 nM, respectively, considerably lower than the Kd values of 50 and 0.25 nM derived from receptor binding analysis. These results indicate that GnRH receptors can be identified in isolated pituitary cells, in which peptide binding is followed by increased cGMP production and LH release. The impaired LH responses in acutely dispersed pituitary cells are not due to the loss of receptor sites but to a reversible postreceptor defect. Occupancy of about 20% of the GnRH-binding sites elicits a near-maximal LH response, indicating the nonlinearity of GnRH-receptor coupling to secretory responses in the cultured gonadotroph.

Animals↗
PubMed1980

Dependence of aldosterone stimulation in adrenal glomerulosa cells on calcium uptake: effects of lanthanum nd verapamil.

The calcium dependence of steroidogenic responses to angiotensin II, potassium, and ACTH was analyzed in isolated adrenal glomerulosa cells incubated with inhibitors of calcium uptake. Both lanthanum and verapamil reduced the stimulation of aldosterone production by each regulator in a dose-dependent manner, with only a moderate decrease in basal steroid production. The stimulation of aldosterone and cAMP production by ACTH was blocked by both antagonists, and the degree of inhibition was dependent on the concentration of ACTH employed. Increasing concentrations of verapamil caused an increase in th ACTH concentration required for half-maximal stimulation as well as a reduction in the maximum production of aldosterone. Aldosterone production by glomerulosa cells in response to angiotensin II or potassium was also decreased by lanthanum and verapamil, with no change in the concentration of angiotensin II required for half-maximal stimulation of steroidogenesis. Stimulation of pregnenolone synthesis by angiotensin II was also inhibited by verapamil, indicating that calcium is required for the action of angiotensin II at an early step in the steroidogenic pathway. The inhibitory action of verapamil upon angiotensin-stimulated aldosterone production was overcome by increasing concentrations of calcium. Neither of the calcium antagonists affected the binding of angiotensin II to glomerulosa cells, placing the calcium requirement for the action of angiotensin II at a postreceptor locus. These results provide further evidence that angiotensin II and potassium increase aldosterone production in adrenal glomerulosa cells through a calcium-dependent mechanism, and indicate that calcium uptake is an essential requirement for the stimulation of aldosterone production by these two effectors.

Adrenal Glands↗
PubMed1980

Calcium-dependent actions of gonadotropin-releasing hormone on pituitary guanosine 3',5'-monophosphate production and gonadotropin release.

The effects of gonadotropin-releasing hormone (GnRH) on cGMP production and LH release in cultured rat pituitary cells are markedly dependent upon the extracellular calcium concentration. The absence of calcium from incubation media caused almost complete loss of the GnRH effects on cGMP production and LH release but did not change the stimulation of cAMP accumulation by GnRH in the pituitary of the adult male rat. In female rat pituitary cells, reduction of the extracellular calcium concentration increased the concentration of GnRH required to produce half-maximal LH release and decreased the maximal gonadotropin output but had no significant effect on basal LH release. The divalent cation ionophore A23187 stimulated LH release, and this action was dependent on extracellular calcium. Both GnRH and A23187 were found to have maximal effects when the calcium concentration was 0.6 mM, and their actions were not additive. The calcium antagonists, verapamil and lanthanum, caused concentration-dependent inhibition of the actions of GnRH, with half-maximal blockade values of 10(-5) and 3 X 10(-6) M, respectively, and had no effect on basal LH release. The binding of a radioiodinated GnRH analog, [D-Ser(t-Bu)6]des-Gly10-GnRH-N-ethylamide, to pituitary GnRH receptors was unchanged in the absence of extracellular calcium. These observations demonstrate that stimulation of pituitary cGMP production and LH release by GnRH is dependent on extracellular calcium. The site at which calcium is required during GnRH action is at a postreceptor locus before cGMP formation.

Animals↗
PubMed1979

Gonadotropin-releasing hormone analogue binds to luteal cells and inhibits progesterone production.

Although gonadotropin-releasing hormone (GnRH) is believed to mediate the hypothalamic control of pituitary gonadotropin secretion, continuous or repeated administration of GnRH or its agonist analogues has been shown to cause paradoxical antifertility effects in several species, including primates. GnRH-induced interruption of reproductive cycles and pregnancy is associated with diminished progesterone production, implying defective function of the corpus luteum. These luteolytic effects have been attributed to the well recognized desensitising actions of elevated luteinising hormone (LH) levels on ovarian LH receptors and steroidogenesis, subsequent to GnRH-induced gonadotropin release from the anterior pituitary. However, treatment with high doses of exogenous LH did not cause suppression of serum progesterone levels during early pregnancy in rats, whereas a highly active GnRH analogue was effective in this regard. These observations suggested that GnRH and its agonist analogues, given in high or sustained doses, can exert a direct action on the ovary that is independent of the pituitary. This hypothesis was further supported by the ability of GnRH and its agonists to inhibit human chorionic gonadotropin (HCG)-induced ovarian and uterine weight gain in hypophysectomised rats and to delay the onset of puberty in intact female rats. Also, GnRH and its agonist analogues have recently been shown to inhibit steroidogenesis induced by follicle-stimulating hormone (FSH) in cultured granulosa cells, confirming the direct action of such peptides on the ovarian follicle. The marked inhibitory effects of GnRH and its agonists on corpus luteum function suggest that these compounds could exert direct actions by binding to specific receptors on luteal cells. The present experiments, which examine the effects of GnRH agonists on luteal steroidogenesis, demonstrate the existence of such actions and their mediation by specific high-affinity receptor sites present in luteal cell membranes.

Animals↗
PubMed1979

The role of cyclic AMP in aldosterone production by isolated zona glomerulosa cells.

The role of cyclic AMP in the regulation of aldosterone production by adrenocorticotropic hormone (ACTH), angiotensin II (A II), potassium, and serotonin was examined in collagenase-dispersed adrenal glomerulosa cells. The ability of 8-bromo cyclic AMP and choleragen to stimulate maximum aldosterone production indicated that cyclic AMP could act as second messenger for certain of the aldosterone-stimulating factors. The actions of ACTH and choleragen on aldosterone and cyclic AMP production were correlated in dog and rat cells, and a similar relation was seen during stimulation of rat cells by serotonin. In contrast, A II and potassium did not cause changes in cyclic AMP formation while stimulating aldosterone production. Intracellular and receptor-bound cyclic AMP were increased 3-fold by 10(-7) M ACTH but not by A II. Addition of a phosphodiesterase inhibitor increased the magnitude of the cyclic AMP response to ACTH but did not change the lack of stimulation by A II or potassium. In dog cells, the effects of A II and potassium on aldosterone production were partially additive to those of ACTH, choleragen, and 8-bromo cyclic AMP. In contrast, no additivity was observed between A II and potassium, or between combinations of the cyclic AMP-dependent stimuli. These results indicate that the actions of ACTH on aldosterone secretion are mediated by cyclic AMP formation, whereas A II and potassium stimulate aldosterone production through an independent mechanism. The lack of additivity between steroid responses to A II and potassium suggests that these factors could share a common mode of action on steroidogenesis in zona glomerulosa cells.

Adrenal Cortex↗
PubMed1979

Hormonal regulation of peptide receptors and target cell responses.

Regulation of plasma membrane receptors for peptide hormones by the prevailing ligand concentration often causes altered target cell function. Receptor number is determined by hormone-induced changes in membrane conformation, irreversible ligand binding, and processing of ligand-receptor complexes during hormone action.

Adenylyl Cyclases↗