Search PubMed⌕ Search

Biomedical subjects

K J Catt

Publications and source records attributed to K J Catt.

At least 343 records · Page 19Linked to original sources
PubMed1981

Induction and maintenance of gonadotropin and lactogen receptors in hypoprolactinemic rats.

The effect of 2-bromo-alpha-ergocriptine (BR)-induced hypoprolactinemia on the induction and maintenance of testicular gonadotropin and lactogen receptors was studied in 60-day-old rats after receptor regulation by a gonadotropin-releasing hormone agonist analog [[D-Ser-(tBu)6]des-Gly10-GnRH N-ethylamide (GnRH-A)] and in young animals during sexual maturation. In adult animals, BR treatment delayed the reappearance of LH binding in the testis after GnRH-A injection, but had no effect on the recovery of lactogen binding. BR treatment also inhibited the increase of LH binding that occurred in control animals during the experimental period, but did not affect lactogen binding. Furthermore, BR potentiated the effect of GnRH-A on the decrease of Leydig cell testosterone synthesis observed 2 days later in vitro. Eight days after GnRH-A injection, concomitant BR treatment significantly inhibited the recovery of Leydig cell cAMP production. In peripubertal (25- to 46-day-old) animals, BR diminished the normal rise in testicular LH receptors, but did not affect the increase in lactogen receptors. Serum testosterone levels and other features of pubertal development, such as balano-preputial separation and spermatogenesis, were unaffected by hypoprolactinemia. In neonatal female animals, significant lactogen binding was detected at 3 days of age, whereas hCG binding was not demonstrable until 9 days after birth. These findings indicate that the expression of lactogen receptors precedes that of LH receptors in the developing gonad, and that the increase of LH binding in the testis during pubertal development requires normal circulating PRL levels. In adult animals, hypoprolactinemia potentiates GnRH-A-induced desensitization of steroidogenesis and cAMP formation, as well as LH receptor down-regulation, delaying the recovery of these phenomena. Although decreased serum PRL levels were associated with a marked reduction in testicular LH receptors both during development and in adult life, the absence of changes in lactogen receptors indicates that the latter sites are largely independent of the circulating PRL concentration.

Animals↗
PubMed1980

Solubilization and characterization of adrenal and uterine angiotensin II receptors after photoaffinity labeling.

The physical characteristic of the receptors for angiotensin II in dog adrenal cortex and uterus were determined after affinity labeling. 125I-nitro-5-azido-benzoyl-angiotensin II, a photosensitive angiotensin II analogue which retained aldosterone-stimulating activity, was used to couple the octapeptide specifically and irreversibly to its membrane receptors. After solubilization with Triton X-100, the covalent hormone . receptor complex was analyzed by gel filtration and sucrose density gradient centrifugation. Two radioactive species were consistently observed, with calculated Mr values of 126,000 +/- 10,000 and 64,500 +/- 11,000. the elution profiles of solubilized adrenal and uterine particles were almost identical. When the solubilized complexes were subjected to sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis, a single radioactive band was detected upon autoradiography, with Mr - 65,000 +/- 6,000 for adrenal cortex and 68,000 +/- 7,000 for myometrium. These results indicate that the receptors for angiotensin II in adrenal cortex and uterus are composed of two subunits of similar molecular weight, and that the common functional properties of the receptors from both tissues are probably related to their similar physicochemical characteristics.

Adrenal Cortex↗
PubMed1980

Lactogenic receptor regulation in hormone-stimulated steroidogenic cells.

Receptor sites for lactogenic hormones such as prolactin (PRL), human growth hormone (HGH), and placental lactogens, are widely distributed in mammalian tissues, including mammary glands, steroid-secreting cells of the adrenal, testis, and ovary, and target cells of steroid hormone action such as liver, prostrate, and kidney. Although the biological functions of lactogen binding sites remain uncertain, a relationship between prolactin and lipoprotein metabolism is implied by the occurrence of prolactin receptors in steroidogenic cells of the gonads and adrenal, and by the ability of prolactin to increase esterified cholesterol in the testis. Recently, loss of testicular prolactin receptors has been observed following elevation of circulating luteinising hormone (LH) concentrations by the gonadotropin releasing hormone (GnRH) and its agonist analogues. The hormone dependence of lactogen receptor sites in steroid-secreting cells was further analysed in rat testis, ovary, and adrenal glands after treatment with the respective trophic hormones, gonadotropin and ACTH. In each of these tissues, rapid and transient loss of lactogen receptors was observed after trophic hormone stimulation. These findings indicate that increased turnover of lactogen receptors is an important component of the target-cell response, and suggest that prolactin receptors might be involved in the transport of lipoprotein precursors for steroid biosynthesis.

Adrenal Glands↗
PubMed1980

Independent actions of gonadotropin releasing hormone upon cyclic GMP production and luteinizing hormone release.

Gonadotropin releasing hormone (GnRH) and its potent analog [D-Ser(tBu)6]des-Gly10-GnRH N-ethylamide elevate pituitary cyclic GMP levels while stimulating gonadotropin release in cultured pituitary cells. Addition of mycophenolic acid to pituitary cell cultures decreased basal and GnRH-induced cGMP production to undetectable levels, but did not reduce basal or GnRH-stimulated luteinizing hormone (LH) release. Elevation of endogenous cGMP levels by sodium nitroprusside, or addition of cGMP or its potent derivatives, was also without effect on basal or GnRH-stimulated LH release. These findings demonstrate that the elevation of intracellular cGMP during GnRH action does not mediate the release of LH by pituitary cells.

Animals↗
PubMed1980

Fluorescence localization of luteinizing hormone/human chorionic gonadotropin uptake in the primate ovary: characterizatin of the preovulatory ovary.

A fluorescent derivative of human chorionic gonadotropin (hCG) for binding studies was prepared by conjugation of hightly purified hCG with fluorescein isothiocynate (FITC-hCG) in a molar ratio of 3:1. The resulting FITC-hCG conjugate retained full cross-reactivity with antibodies directed against intact hCG, the hCG beta-subunit, the carboxyl-terminal peptide sequence of beta-hCG. The fluorescent hormone retained binding activity similar to that of native hCG, and the capacity to induce progesterone production from primate corpora luteal cells in vitro. After intravenous administration to female rhesus monkeys, FITC-hCG was localized within the theca cell layer of certain antral follicles, including the dominant follicle, but no fluorescence was noted around preantral follicles. Areas of fluorescence were also localized to discrete groups of interstitial gland cells in the stroma. The degree of fluorescence associated with these cells was indistinguishable from that observed in the thecal cells. The development of a fluorescent derivative that is biologically and immunologically similar to native hCG has permitted differential microscopic localization of luteinizing hormone/hCG uptake in the preovulatory ovary.

Animals↗
PubMed1980

Hormone-induced guanyl nucleotide binding and activation of adenylate cyclase in the Leydig cell.

The adenylate cyclase activity of Leydig cell homogenates and membrane fractions is highly dependent on guanyl nucleotides, and enzyme responses to luteinizing hormone or human chorionic gonadotropin are small in the absence of guanyl nucleotides. However, in the presence of 10 microM guanosine 5'-[beta, gamma-imido]triphosphate Gpp[NH]p, both hormones consistently stimulated testicular adenylate cyclase activity by up to 200%. Leydig cell membranes bound [3H]Gpp[NH]p at 30 degrees C with high affinity (Ka = 1.5 X 10(7) M-1) and binding capacity of 60 pmol/mg of protein. During kinetic studies, the association rate constant was 1.7 X 10(6) M-1 min-1, and the dissociation constant was 0.038 min-1. In the presence of gonadotropin (10 pM to 10 nM), concentration-dependent increases of 40% to 100% in Gpp[NH]p binding were observed in Leydig cell membranes. Kinetic studies showed that gonadotropin decreased the association rate constant to 0.73 X 10(6) M-1 min-1 and the dissociation rate constant to 0.017 min-1, with no effect on the equilibrium binding constant. Thus, the increase in Gpp[NH]p binding was not due to a change in receptor affinity but was attributable to increased availability of nucleotide binding sites. The 50% effective dose for adenylate cyclase activation by gonadotropin in the presence of Gpp[NH]p was identical with that observed for gonadotropin-induced binding of the GTP analog (50 nM). Gonadotropin-induced binding of Gpp[NH]p in Leydig cell membranes may represent interaction with the guanyl nucleotide regulatory site during hormonal activation of adenylate cyclase.

Adenylyl Cyclases↗
PubMed1980

Direct inhibition of testicular function by gonadotropin-releasing hormone: mediation by specific gonadotropin-releasing hormone receptors in interstitial cells.

Agonist analogs of gonadotropin-releasing hormone (GnRH) have been shown to exert antigonadal effects in male and female animals. In hypophysectomized male rats treated with follicle-stimulating hormone, administration of a potent GnRH agonist caused depletion of luteinizing hormone and prolactin receptors and marked suppression of serum testosterone levels. The possibility that such direct effects of GnRH agonists on testicular function could be expressed through specific receptors located in the interstitial cells of the testis was supported by the selective concentration of a 125I-labeled GnRH agonist by the testis in vivo. Specific receptors for the releasing hormone were demonstrated in testis particles and dispersed interstitial cells by direct binding analysis with the 125I-labeled GnRH agonist. The binding affinity (Ka = G X 10(9) M-1) and peptide specificity of the testicular GnRH binding sites were similar to those of anterior pituitary and ovarian GnRH receptors. The presence of GnRH receptors in the testis indicates that these sites mediate the direct inhibitory actions of GnRH agonists upon testicular endocrine function.

Animals↗
PubMed1980

Estrogen dependence of a gonadotropin-induced steroidogenic lesion in rat testicular Leydig cells.

Leydig cells isolated from the testes of rats treated with intravenous exogenous gonadotropin (hCG) or subcutaneous gonadotropin-releasing hormone (GnRH) show markedly decreased luteinizing hormone (LH) receptors and a partial block in testicular 17,20 desmolase activity. In contrast, Leydig cells from animals with equivalent degrees of LH receptor loss induced by subcutaneous hCG treatment show no change in 17,20 desmolase activity. These findings indicated that the acuteness of gonadotrophic stimulation, rather than the extent of LH receptor loss, was responsible for the steroidogenic lesion. A role of estradiol in the enzymatic block produced in vivo by acute elevation of circulating gonadotropin (intravenous hCG or GnRH-stimulated endogenous LH) was suggested by rapid elevations of testicular 17beta-estradiol within 30 min after intravenous hCG, whereas more gradual increases in estradiol occurred 4-8 h after subcutaneous hCG. The inhibitory effect of endogenous estrogen on testicular steroidogenesis was confirmed by the ability of an estrogen antagonist (Tamoxifen) to prevent the reduction of testosterone responses caused by intravenous hCG and subcutaneous GnRH. In addition, Tamoxifen significantly increased the number of LH receptors in Leydig cells from both control and gonadotropin-desensitized animals. These findings indicate that the acute elevations of intratesticular estrogen produced by treatment with hCG or GnRH are responsible for the steroidogenic lesion seen in gonadotropin-desensitized Leydig cells. These results also suggest that locally produced estrogens contribute to the regulation of testicular LH receptors and 17,20 desmolase activity.

Aldehyde-Lyases↗
PubMed1980

Receptor-binding activity of highly purified bovine luteinizing hormone and thyrotropin, and their subunits.

Highly purified preparations of bovine TSH (bTSH) and LH (bLH) and their subunits have been obtained by affinity chromatography using immobilized antibodies directed against counterpart subunits. The purified preparations were assessed for biological activity in radioligand-receptor assays for TSH and LH. After affinity purification against bLH beta, a TSH preparation whose initial potency in the LH assay had been 0.15% that of LH, failed to compete with [125I]LH in amounts up to 100 microgram. Thus, it appears that bTSH does not bind to LH receptors in the rat testis and that interaction of less purified TSH with gonadotropin receptors is attributable to LH contamination. In contrast, LH, whose initial potency in the TSH receptor assay was 0.6% that of TSH, retained a potency of 0.004% of TSH (equivalent to 3.6 mU/mg) after immunoadsorption by anti-bTSH beta. The retention of TSH receptor-binding activity by affinity-purified LH indicates that the LH molecule (like hCG) has a low intrinsic thyroid-stimulating activity. Affinity-purified LH subunits have little or no demonstrable affinity for the LH receptor in vitro. Affinity-purified TSH subunits and affinity-purified LH, however, exhibit very weak receptor-binding activity in the TSH radioligand receptor assay. An evaluation of the capacity of the immunoadsorbents to remove TSH from artificial mixtures suggests that the residual binding does not result entirely from contamination, and therefore, that alpha-subunits as well as LH have some intrinsic TSH-binding activity.

Animals↗
PubMed1980

Modulation of serum and pituitary luteinizing hormone bioactivity by androgen in the rat.

The biological and immunological activities of serum and pituitary LH were analyzed in normal and castrated rats using the rat interstitial cell testosterone assay and RIAs for intact rat LH (rLH), rLH alpha, and rLH beta. After castration, the bioactivity to immunoactivity ratio of both serum and pituitary LH decreased by about 50% between the 5th and 25th days and returned to normal by 60 days. This decrease in the bioactivity to immunoreactivity ratio of LH in castrated males was not due to increased subunit production and was prevented by the administration of testosterone propionate (50 micrograms/day) from the time of castration. These observations indicate that androgens of their metabolites modify the bioactivity of the circulating and stored forms of the LH molecule.

Animals↗