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K J Catt

Publications and source records attributed to K J Catt.

At least 235 records · Page 13Linked to original sources
PubMed1986

Involvement of protein kinase C in the regulation of adrenocorticotropin release from rat anterior pituitary cells.

The involvement of protein kinase C in normal corticotroph function was studied by analysis of the effects of the phorbol ester derivative phorbol 12-myristate-13-acetate (PMA) and the synthetic diacylglycerol dioctanoylglycerol (DOG) on basal and stimulated ACTH release in cultured rat anterior pituitary cells. Incubation of rat pituitary cells with increasing concentrations of PMA or DOG caused dose-related increases in ACTH release up to 13.4 +/- 2.1- and 10.1 +/- 0.9-fold, respectively, similar to that caused by CRF (9.8 +/- 1.6-fold). Also, stimulation of endogenous diglyceride formation by phospholipase C (100 mU/ml) stimulated ACTH release by 2.5 +/- 0.1-fold. In cells incubated with maximum stimulatory concentrations of CRF (10 nM) or 8-bromo-cAMP (8-Br-cAMP; 5 mM), addition of either 100 microM DOG or 100 nM PMA caused significantly higher ACTH responses than those obtained with CRF, 8-Br-cAMP, DOG, or PMA alone. 8-Br-cAMP (5 mM) and 10 nM CRF significantly increased the effect of 100 nM PMA by 1.4 +/- 0.2- and 1.5 +/- 0.1-fold, respectively. Combinations of 10 nM CRF with either vasopressin (VP) or angiotensin II (AII) increased ACTH secretion to values higher than those produced by CRF, VP, or AII alone. However, addition of maximal stimulatory concentrations of VP or AII (10 nM) did not further increase the effects of either PMA alone or PMA/CRF combinations, indicating that their mechanisms of action may be similar to that of PMA. These results indicate that in addition to the established cAMP-dependent mechanism, stimulation of ACTH release in normal pituitary cells may be elicited by activation of protein kinase C. The evidence also suggests that protein kinase C is involved during stimulation of ACTH release by the cAMP-independent regulators VP and AII and in the synergistic effects of VP and AII with CRF on the corticotroph.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1986

Selective enhancement of angiotensin II- and potassium-stimulated aldosterone secretion by the calcium channel agonist BAY K 8644.

Recent studies with dihydropyridine calcium channel antagonists have indicated that voltage-sensitive calcium channels (VSCC) play a major role in the control of aldosterone secretion. The modulation of VSCC by physiological regulators of zona glomerulosa function was further evaluated by analysis of the actions of the dihydropyridine calcium channel agonist BAY K 8644 (BK 8644) on basal and stimulated aldosterone production in isolated rat glomerulosa cells. In the presence of normal K+ concentrations (3.5-4.5 mM), only high concentrations of BK 8644 (greater than or equal to 100 nM) stimulated aldosterone secretion. However, addition of 10 nM BK 8644 markedly enhanced steroid production (70% over control) in cells stimulated by incubation in 7.5 mM K+ or 0.1 nM angiotensin II (AII). Greater enhancement was achieved with 1 microM BK 8644, with aldosterone secretion 150% and 300% above control levels for K+ and AII, respectively. In AII-stimulated cells, 30 nM BK 8644 enhanced aldosterone secretion at all peptide concentrations studied, including a 70% increase in the maximum steroid response, with no change in sensitivity to AII. In K+-stimulated cells, the effects of BK 8644 were dependent on the medium concentration of K+. At submaximally stimulating K+ concentrations (less than 9 mM), 30 nM BK 8644 increased the sensitivity of glomerulosa cells to K+ with no change in the maximal aldosterone response. However, at supramaximally stimulating concentrations of K+ (greater than 10 mM), BK 8644 reduced aldosterone production by 50%. In contrast to the effects of BK 8644 on cells stimulated with K+ or AII, the channel agonist had no effect on the action of ACTH. The ability of BK 8644 to enhance the maximum aldosterone response to AII suggests that AII, unlike K+, does not fully activate the Ca2+ influx pathway that leads to aldosterone secretion. Since BK 8644 is believed to facilitate Ca2+ influx primarily through previously activated channels, these results suggest that VSCC in the rat glomerulosa cell are partially operative under basal conditions, and that the same types of channels are further activated by AII and K+.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Inhibition of luteinizing hormone release by morphine and endogenous opiates in cultured pituitary cells.

Morphine sulfate was found to have a direct inhibitory effect on both basal and GnRH-stimulated LH release by cultured rat pituitary cells. The inhibitory effect of morphine on LH release was prevented by the opiate antagonist naltrexone, and treatment of cells with naltrexone or beta-endorphin antiserum significantly increased basal LH release. Also, incubation of pituitary cells with CRF caused a significant decrease in basal LH release, an effect that was reversed by naltrexone. Saturable opiate-binding sites were demonstrated in enriched gonadotrophs by [3H]etorphine binding studies. The ability of morphine to inhibit gonadotropin secretion through a direct action on pituitary opiate receptors suggests that long term exposure to exogenous opiates may suppress reproductive function at the hypophyseal level. In addition, the converse effects of CRF and naltrexone or beta-endorphin antiserum on LH release indicate that intrapituitary opioid peptides could exert a paracrine inhibitory action on the gonadotroph.

Animals↗
PubMed1986

Biosynthesis of cellular and secreted proteins during follicle-stimulating hormone-induced granulosa cell differentiation.

The synthesis of cellular and secreted proteins by differentiating granulosa cells from diethylstilbestrol-treated immature rats was studied by one- and two-dimensional polyacrylamide gel electrophoresis. In cultured granulosa cells, FSH altered the relative biosynthesis of specific cellular and secreted proteins in a concentration- and time-dependent manner. The incorporation of [35S]methionine into cellular proteins of Mr 42,000, 48,000, and 58,000 was enhanced by increasing amounts of the gonadotropin, whereas the labeling of a 44,000 Mr protein was reduced. Similarly, FSH increased the labeling of secreted proteins with relative Mr of 16,000, 17,000, 20,000, 25,000, 36,000, 41,000, 46,000, 111,000, and 153,000, and decreased that of proteins with Mr of 38,000, 48,000, 191,000, and 250,000. The expression of specific proteins was related to the degree of cellular maturation, since some proteins were newly synthesized during the early stages of granulosa cell development (less than 6 h), whereas others were more evident in the middle (24 h) or later (48 h) phases of culture. Also, the level of specific protein synthesis was variable since certain proteins were progressively produced during culture, and the biosynthesis of others fluctuated or was reduced during development. The effects of FSH on protein synthesis were mimicked by other cAMP-inducing ligands, including cholera toxin, forskolin, and 8-bromo-cAMP. Removal of FSH at 24 h of culture was followed by reversion of the protein biosynthetic pattern at 48 h to that of control cells, indicating that continued exposure to the gonadotropin is required during development. Cells cultured in the absence of ligands for 24 h synthesized proteins characteristic of differentiated cells when subsequently cultured with forskolin. These results indicate that FSH selectively alters the biosynthesis of cell-associated and secreted proteins during granulosa cell maturation. The characterization of these gene products and the mechanisms controlling their expression should ultimately clarify the sequential events involved in the hormonal regulation of granulosa cell development.

Animals↗
PubMed1986

Biphasic inhibition of adrenocorticotropin release by corticosterone in cultured anterior pituitary cells.

The inhibition of ACTH secretion by glucocorticoids in vivo is biphasic, with rapid early suppression followed by transient recovery and a late inhibitory phase. To evaluate whether this biphasic effect of glucocorticoids occurs at the pituitary level, the effects of corticosterone (B) on stimulated ACTH release were analyzed in rat anterior pituitary cell cultures. Preincubation with 1 microM B inhibited the ACTH response to 10 nM CRF in a biphasic manner, with rapid inhibition after 10-40 min of preincubation, followed by partial recovery between 40-80 min, and a later phase of inhibition after 80-140 min. Preincubation with B for 40 or 120 min caused a dose-dependent suppression of CRF-stimulated ACTH release, with ED50 values of 416 +/- 21 and 45 +/- 12 nM B, respectively. Pretreatment with B also caused a biphasic inhibitory effect on the stimulatory action of vasopressin, angiotensin II, and norepinephrine on ACTH release. However, addition of these stimuli in combination with CRF surmounted B inhibition of CRF-stimulated ACTH release. B also inhibited the ACTH-releasing effects of postreceptor stimuli, including 8-bromo-cAMP, phorbol 12-myristate 13-acetate, and 1,2-dioctanoylglycerol. In the presence of cycloheximide (10 microM), the early inhibitory effect of B was unchanged, but the delayed effect was decreased. Whereas preincubation with B for 40 min inhibited ACTH release, but not total intracellular plus released ACTH, preincubation for 120 min decreased both released and total ACTH. These findings demonstrate that the two inhibitory effects of B on ACTH release differ in their kinetics, steroid sensitivity, and dependence on protein synthesis. The inhibitory effect of B on ACTH responses to stimuli with different mechanisms of action suggests that the suppressive effects of B are mainly exerted at a site distal to the formation of the second messengers involved in hormonal activation of ACTH release.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1986

Role of arachidonic acid in the regulation of adrenocorticotropin release from rat anterior pituitary cell cultures.

In addition to cAMP-dependent mechanisms, stimulation of pituitary ACTH secretion by various stimuli, including CRF, may involve phospholipid and arachidonic acid turnover. To determine the role of phospholipase A2 activation in corticotroph function, we studied the effect of exogenous arachidonic acid, phospholipase A2, and the phospholipase A2 activator melittin on ACTH release in cultured rat anterior pituitary cells. Incubation with 1-100 micron arachidonic acid, 0.01-1 micron melittin, 0.1-10 U/ml phospholipase A2, and 0.01-10 nM CRF caused dose-dependent increases in ACTH release to 8.1 +/- 1.1- (+/- SE), 16.2 +/- 0.9-, 13.6 +/- 1.2-, and 2.9 +/- 0.3-fold; respectively. The participation of the major pathways of arachidonic acid metabolism in the control of ACTH release was analyzed in cells treated with nordihydroguaiaretic acid, a lipoxygenase inhibitor; indomethacin, a cycloxygenase inhibitor; and 5,8,11,14-eicosatetraynoic acid, an inhibitor of both pathways. The effects of arachidonic acid, melittin, and CRF were partially blocked by 10 micron nordihydroguaiaretic acid and 5,8,11,14-eicosatetraynoic acid, but were significantly enhanced by 10 micron indomethacin. These results suggest that arachidonic acid is mainly metabolized through the lipoxygenase pathway to a stimulatory metabolite and, to a lesser extent, through the cycloxygenase pathway to an inhibitory metabolite. Arachidonic acid release from anterior pituitary cells labeled with [3H]arachidonic was analyzed during cell column perifusion and stimulation by CRF and other secretagogues. Two-minute pulses of CRF (10 nM), vasopressin (10 nM) and phorbol 12-myristate 13-acetate (100 nM) caused immediate 1.5- to 2-fold increases in [3H]arachidonic acid release, and melittin (100 nM) caused a 5-fold increase in [3H]arachidonic acid release. The ability of both exogenously added and endogenously generated arachidonic acid to stimulate ACTH secretion, together with the stimulation of arachidonic acid release by ACTH secretagogues and the attenuation of stimulated ACTH release by lipoxygenase blockers, indicate that lipoxygenase products of arachidonic acid metabolism participate in the control of ACTH secretion.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1986

Pituitary binding and internalization of radioiodinated gonadotropin-releasing hormone agonist and antagonist ligands in vitro and in vivo.

In rat pituitary gonadotrophs, the rates of binding and endocytosis of two GnRH superagonist analogs, [D-Ala6,Pro9-NEt]GnRH and [D-Lys6,Pro9-NEt]GnRH, were compared with those of the potent antagonist analog [N-acetyl-D-pCl-Phe1,2,D-Trp3,D-Lys6,D-Ala10]GnRH by quantitative electron microscopic autoradiography. In dispersed pituitary cells, the two agonist analogs showed similar binding kinetics and comparable degrees of sequestration, as measured by their resistance to dissociation by low pH buffer. However, quantification of silver grain localization suggested that cellular internalization of the [D-Ala6]GnRH agonist increased more rapidly than that of the [D-Lys6]GnRH analog. These discrepancies, and the finding that a larger amount of the specifically bound 125I-[D-Ala6]GnRH agonist was removed during glutaraldehyde fixation, indicated that the proportional internalization of this analog was over estimated by quantitative autoradiography owing to loss of cell surface-bound radioligand. We, therefore, employed radioiodinated D-Lys6-substituted analogs to analyze the receptor binding and cellular uptake of GnRH agonist and antagonist derivatives in vivo. After iv injection, a high proportion of the 125I-[D-Lys6]GnRH agonist was translocated into pituitary gonadotrophs within 60 min, whereas the D-Lys6 antagonist was predominantly associated with the plasma membrane during that time. Four hours after injection of the antagonist, an appreciable proportion of silver grains was associated with intracellular organelles, and this trend increased progressively at later time points. The relatively prolonged cellular processing of the GnRH antagonist is consistent with in vivo binding kinetics, and its slower internalization may reflect the basal rate of GnRH receptor turnover in the cell membrane. In addition, the marked difference between the rates of internalization of the bound [D-Lys6]GnRH agonist and antagonist ligands supports the proposal that receptor activation is responsible for the rapid endocytosis of agonist ligands by the GnRH-stimulated pituitary gonadotroph.

Animals↗
PubMed1986

Effects of 17 beta-estradiol on angiotensin II receptors and prolactin release in cultured pituitary cells.

Angiotensin II (AII) binds to specific receptors in the lactotroph and stimulates PRL secretion from isolated rat pituitary cells. Since estrogens exert major regulatory actions on PRL secretion, the effects of estradiol (E2) on pituitary AII receptors and PRL responses were studied in vivo and in cultured rat anterior pituitary cells. In female rats, treatment with E2-containing Silastic capsules for 4 days caused a significant increase in PRA from 1.3 to 3 ng/ml X min and a 38% decrease in the binding of [125I]AII to anterior pituitary membrane-rich fractions (P less than 0.01). In vitro studies showed that treatment of cultured anterior pituitary cells with 1 nM E2 for 4 days caused a 57 +/- 6% decrease in AII receptor concentration with no change in binding affinity. Reduction of AII receptors by E2 in 4-day cultures was dose dependent and was demonstrable with E2 concentrations that occur in plasma during the estrous cycle (0.01-1 nM). The decrease in AII receptors in cells incubated with 1 nM E2 was near maximum after 24 h of culture, and results were similar when receptor concentrations were calculated per unit protein or per cell. Despite the substantial decrease in AII receptors, E2 treatment did not specifically decrease the responsiveness of the pituitary cells to AII stimulation. Thus, PRL responses to AII (10 nM) or TRH (100 nM) were unchanged after 1 day of E2 treatment and were increased after 4 days of treatment. These findings demonstrate that E2 has a direct inhibitory action on expression of pituitary AII receptors that is not accompanied by a decrease in AII-stimulated PRL secretion. In the rat pituitary, estrogen modulation of postreceptor events is the predominant determinant of lactotroph responsiveness during stimulation of PRL release by AII.

Animals↗
PubMed1986

Characterization of a gonadotropin-releasing hormone receptor site in term placenta and chorionic villi.

The properties of GnRH receptor sites in the human placenta were analyzed by binding studies performed in particulate and solubilized receptor preparations. The binding affinities (Ka) of the membrane receptor of term placenta for the GnRH superagonists [D-Lys6]- and [D-Ala6]des-Gly10- GnRH-N-ethylamide were 1.6 X 10(6) and 5.4 X 10(5) M-1, respectively. The binding affinities of native GnRH and a potent GnRH antagonist were similar to those of the superagonists (1.1 and 2.0 X 10(6) M-1, respectively). The placental sites could be solubilized by extraction with the detergent 3-[(3-cholamidopropyl) dimethylammonio] 1-propane sulfonate, with retention of 40-45% of the specific binding activity, though with a significant decrease in binding affinity. The sites were also solubilized with sodium dodecyl sulfate after covalent labeling with a photoreactive 125I-labeled [D-Lys6] GnRH agonist derivative. Analysis of the solubilized hormone-receptor complex on polyacrylamide gradient gels showed a single band of 53,700 mol wt, similar to the mol wt of the pituitary GnRH receptor in other species. It is clear that the placental receptor differs markedly from the GnRH receptor of the pituitary gland in its low binding affinity and lack of selectivity for GnRH analogs. However, it is possible that the human placental receptor for GnRH could serve as a low affinity regulatory site for locally formed GnRH or related low affinity regulatory site for locally formed GnRH or related peptides within the placenta, and that the placental GnRH system has a significant role in the maintenance of pregnancy.

Binding, Competitive↗
PubMed1986

Kinetic and autoradiographic studies on binding of hCG to the testicular LH receptors of neonatal rats.

The properties of hCG binding to LH receptors of the neonatal (5-day-old) rat testis were analysed and compared with those of the adult testis. The equilibrium association constants (Ka) of hCG-binding were similar at both ages, 2-4 X 10(10) M-1. In contrast, kinetic binding studies revealed that the association and dissociation rate constants of hCG binding were more rapid in the neonatal testis. Likewise, it was observed that the progression from loose (easily dissociable) to tight (non-dissociable) binding was less complete in the young than in the adult testis. Autoradiography of 125I-labelled hCG binding to interstitial cell suspensions at the two ages showed that the gonadotrophin binding per Leydig cell was about 50% lower in the neonatal testis. Conversely, since the surface area of adult Leydig cells was about 4-fold larger, the receptor density appeared to be higher in the neonatal Leydig cells. The rapid recovery of LH receptors after hCG stimulation, typical of the neonatal cells, was due to rapid replenishment of binding in the cells initially occupied by the injected hormone, rather than to an hCG-induced increase of Leydig cell number. Finally, in-vivo experiments with cycloheximide revealed that the rapid recovery of LH receptors was dependent on protein synthesis. These differences in the kinetics of neonatal testicular LH receptor turnover may be involved in the unique functional features of the fetal-neonatal growth phase of rat testicular Leydig cells.

Animals↗
PubMed1986

Effects of long- and short-term gonadectomy on the hypothalamo-hypophysial (LH-releasing hormone-LH) system in oestrogen-treated male and female rats.

Considerable differences have previously been found in the hypothalamo-hypophysial responsiveness to oestrogen, depending upon the time between gonad removal and exposure to oestrogen. In the present study a detailed analysis was made of some of the differences which may exist in pituitary LH-releasing hormone (LHRH) receptors and the amount of LH released in response to electrochemical depolarization of the medial preoptic area after 2 or 7 days of oestradiol treatment of long- and short-term gonadectomized male and female rats. The pituitary glands of long-term gonadectomized males and females secreted more LH in response to two pulse injections of LHRH than did short-term gonadectomized rats. The amount of LH released on day 2, however, was equivalent to that secreted after 7 days of oestradiol treatment. Moreover, long-term gonadectomized males and females had equivalent LHRH receptor concentrations, which were greater than those of short-term gonadectomized animals. Peak serum LH concentrations observed after preoptic stimulation were equivalent in short- and long-term castrated rats after 2 days of oestrogen exposure. Serum LH concentrations following preoptic stimulation in short-term gonadectomized males and females were significantly greater on day 7 than on day 2 of oestradiol treatment, whereas in long-term gonadectomized animals the stimulated release of LH was equivalent both in magnitude and time of peak release on both days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Angiotensin II receptors in the kidney.

Angiotensin II (AngII) receptors have been localized in rat kidney by using the high-affinity agonist analog 125I-labeled [Sar1]AngII as a probe for in vitro autoradiography. Receptors were associated with four morphologically distinct patterns of distribution. First, a high density of receptors occurs in glomeruli. These are diffusely distributed, consistent with a mesangial localization. AngII receptor density shows a cortical gradient, which is highest in superficial and midcortical glomeruli and lowest in juxtamedullary glomeruli. Receptors associated with both superficial and deep glomeruli show down-regulation during low-sodium intake. Second, low levels of tubular AngII binding were seen in the outer cortex. Third, a very high density of AngII receptors occurs in longitudinal bands in the inner zone of the outer medulla in association with vasa recta bundles. Receptors in this site also show down-regulation during low dietary sodium intake. Fourth, a moderate density of receptors occurs diffusely throughout the inner zone of the outer medulla in the interbundle areas. These results suggest that AngII exerts a number of different intrarenal regulatory actions. In addition to the known vascular, glomerular, and proximal tubular effects of AngII, these findings focus attention on possible actions of AngII in the renal medulla where it could regulate medullary blood flow and thereby modify the function of the countercurrent concentrating system.

Angiotensin II↗
PubMed1985

Differential actions of phorbol ester and diacylglycerol on inhibition of granulosa cell maturation.

Hormonal induction of granulosa cell maturation is inhibited by phorbol esters and permeant synthetic diacylglycerols, but these activators of protein kinase C differ in their effects on cAMP production and actions. Both agents prevented the induction of luteinizing hormone receptors and progesterone biosynthesis by follicle-stimulating hormone, choleragen, and forskolin, but only diacylglycerol abolished the cAMP responses to these stimuli. Granulosa cell aggregation and aromatase activity were inhibited by phorbol ester but not completely by diacylglycerol. In intact granulosa cells, cytosolic C kinase activity was rapidly decreased by phorbol ester but unaffected by diacylglycerol. Although diacylglycerol has a marked inhibitory action on cAMP production, the more prominent suppression of granulosa cell differentiation by phorbol ester may be related to its rapid and prolonged action on kinase C.

Animals↗
PubMed1985

Binding sites for inositol trisphosphate in the bovine adrenal cortex.

Binding sites for inositol trisphosphate (IP3) have been identified in bovine adrenal cortex, employing [32P]IP3 prepared from human erythrocytes radiolabeled with [32P]ATP. IP3 was bound to adrenal microsomes with high affinity (Kd = 5 nM) and low capacity (186 fmol/mg protein). During kinetic studies, half-maximal binding was reached in less than one min at 4 degrees C, and dissociation was even more rapid with t1/2 of about 10 sec. [32P]IP2 showed no binding to the microsomal sites, which represent putative receptors at which IP3 acts to elevate intracellular calcium concentration during the actions of peptide hormones such as angiotensin II.

Adrenal Cortex↗
PubMed1985

Hormone-induced redistribution of calcium-activated phospholipid-dependent protein kinase in pituitary gonadotrophs.

The distribution of calcium-activated, phospholipid-dependent protein kinase (protein kinase C) between cytosol and membrane fractions was analyzed in cultured pituitary gonadotrophs during treatment with gonadotropin-releasing hormone (GnRH). In pituitary cells purified by centrifugal elutriation, the extent of protein kinase C redistribution during GnRH stimulation was correlated with the enrichment of gonadotrophs. GnRH-stimulated release of luteinizing hormone (LH) from gonadotroph-enriched cells was accompanied by a rapid and dose-dependent decrease in cytosolic protein kinase C and by a corresponding increase in protein kinase C activity in the particulate fraction. Retinal directly inhibited the activity of cytosolic protein kinase C and also attenuated the release of LH from GnRH-stimulated gonadotrophs. These findings, and the ability of GnRH to cause rapid translocation of cytosolic protein kinase C to a membrane-associated form, suggest that hormonal activation of protein kinase C is an intermediate step in the stimulation of pituitary LH secretion by GnRH.

Animals↗
PubMed1985

Newborn and immature rat testes contain gonadotropin-releasing hormone (GnRH) receptors, and their testosterone production is stimulated by a GnRH agonist in vitro.

The possibility of direct gonadal effects of GnRH in the newborn and immature rat testis was studied by two approaches: the presence of specific high-affinity receptors for a GnRH agonist analogue (Buserelin) was studied in animals between the ages of 1 and 60 days; and the effect of Buserelin on testicular testosterone production was studied in vitro. GnRH receptors were found in the testis tissue at all ages studied, and there was a gradual increase in the number of binding sites per testis with advancing age. The highest concentration of GnRH receptors was found in the rat testis tissue on day 1 of life, 3.2 +/- 0.4 fmoles/g tissue (mean +/- SE, n = 5). The binding declined to a nadir, 1.5 +/- 0.5 fmoles/g tissue (in = 10), on day 15 post-partum (p less than 0.05), and thereafter increased again gradually to a level of 2.7 +/- 0.3 fmoles/g (n = 5) on day 60 of life (p less than 0.05). The biphasic concentration curve of GnRH receptors followed closely the volume density of Leydig cells in the developing rat testis. Buserelin at a concentration of 10(-7) M was able to stimulate significantly (p less than 0.01), by 98-146%, the testosterone production of decapsulated testes at all ages studied between 1 and 60 days of life. These results indicate the presence of functional GnRH receptors in the testis tissue of newborn and immature rats.

Animals↗
PubMed1985

GnRH receptors and actions in the control of reproductive function.

The hypothalamic control of reproductive function is expressed through the receptor-mediated actions of GnRH on the pituitary gonadotroph. GnRH receptors in the pituitary gland exhibit prominent variations in number during the ovarian cycle and after changes in steroid feedback, and are modulated by the rate of GnRH secretion from the hypothalamus. In cultured pituitary cells, GnRH receptors undergo down-regulation during exposure to GnRH agonists, followed by a subsequent elevation of sites that is dependent on protein synthesis. GnRH antagonists do not cause receptor down-regulation, but high-affinity antagonist analogs bind for extended periods to cause receptor occlusion and prolonged inhibition of GnRH action. Analysis of the rat pituitary GnRH receptor by photoaffinity labeling reveals two binding subunits of mol. wt 53,000 and 42,000. The receptor-activated processes leading to gonadotropin secretion are highly calcium-dependent, and are initiated by rapid phospholipid hydrolysis with production of arachidonic acid metabolites, diacylglycerol, and inositol phosphates. The role of protein kinase C in gonadotropin secretion is indicated by the ability of phorbol esters and synthetic diacylglycerols to stimulate LH release, the inhibition of protein kinase C and LH release by retinal, and the redistribution of protein kinase C between cytosol and membrane fractions during stimulation of pituitary gonadotrophs by GnRH. It is likely that the effects of arachidonate metabolites are integrated with those of calcium-calmodulin and calcium, phospholipid-dependent protein kinases during the immediate and sustained phases of GnRH-induced gonadotropin secretion.

Animals↗