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At least 955 records · Page 53Linked to original sources
PubMed1995

Insulin treatment (hormonal imprinting) increases the insulin production of the unicellular tetrahymena long term. Is there a simultaneous formation of hormone receptor and hormone?

Insulin treatment of Tetrahymena pyriformis resulted in a long-lasting increase in the insulin content of the cells. After about 200 generations, insulin levels significantly higher than in the control were demonstrated by using a quantitative immunocytochemical method. Although the insulin content fluctuated from day to day, it was always higher in the insulin pre-treated (imprinted) cells than in the controls. The results emphasise the simultaneous stimulation of hormone and receptor formation by hormonal imprinting.

Animals↗
PubMed1996

Negative regulation of the gene for the preprothyrotropin-releasing hormone from the mouse by thyroid hormone requires additional factors in conjunction with thyroid hormone receptors.

To gain additional insights into the negative gene regulatory action by triiodothyronine (T3), we isolated a 2-kilobase pair 5'-flanking region of the mouse preprothyrotropin-releasing hormone (ppTRH) gene and characterized the DNA elements mediating inhibitory regulation by T3 in the promoter region. In GH4C1 cells, the expression of the 2-kilobase pair mouse ppTRH 5'-flanking region fused to the luciferase reporter gene occurred by transfection and was significantly suppressed by T3. In contrast, T3 suppression was not observed in T3 receptor (T3R)-deficient CV-1 cells, suggesting that T3Rs were required for the negative regulation. Cotransfected mouse T3R alpha1, beta1, and beta2 possessed indistinguishable potency for the negative regulation. Deletion analysis localized the element mediating the negative regulation to the region between -83 and +46, and the sequence downstream of the transcription start site (TSS) between +12 and +46 was found to be essential for the inhibitory regulation. In mobility shift assays, only T3R monomers bound to the element containing a T3 response element half-site at -57. No apparent T3R binding was observed to the element downstream of TSS. Neither the T3 response element half-site nor the element downstream of the TSS confer T3 suppression individually in heterologous promoters. These results indicate that the negative regulation of murine ppTRH gene by T3 might be mediated by the cooperation of T3R monomers with unknown factor(s) interacting with the element downstream of the TSS.

Animals↗
PubMed2000

Minimization of parathyroid hormone. Novel amino-terminal parathyroid hormone fragments with enhanced potency in activating the type-1 parathyroid hormone receptor.

The amino-terminal and carboxyl-terminal portions of the 1-34 fragment of parathyroid hormone (PTH) contain the major determinants of receptor activation and receptor binding, respectively. We investigated how the amino-terminal signaling portion of PTH interacts with the receptor by utilizing analogs of the weakly active fragment, rat (r) PTH(1-14)NH(2), and cells transfected with the wild-type human PTH-1 receptor (hP1R-WT) or a truncated PTH-1 receptor which lacked most of the amino-terminal extracellular domain (hP1R-delNt). Of 132 mono-substituted PTH(1-14) analogs, most having substitutions in the (1-9) region were inactive in assays of cAMP formation in LLC-PK1 cells stably expressing hP1R-WT, whereas most having substitutions in the (10-14) region were active. Several substitutions (e.g. Ser(3) --> Ala, Asn(10) --> Ala or Gln, Leu(11) --> Arg, Gly(12) --> Ala, His(14) --> Trp) enhanced activity 2-10-fold. These effects were additive, as [Ala(3),(10,12),Arg(11), Trp(14)] rPTH(1-14)NH(2) was 220-fold more potent than rPTH(1-14)NH(2) (EC(50) = 0.6 +/- 0.1 and 133 +/- 16 micrometer, respectively). Native rPTH(1-11) was inactive, but [Ala(3,10), Arg(11)]rPTH(1-11)NH(2) achieved maximal cAMP stimulation (EC(50) = 17 micrometer). The modified PTH fragments induced cAMP formation with hP1R-delNt in COS-7 cells as potently as they did with hP1R-WT; PTH(1-34) was 6,000-fold weaker with hP1R-delNt than with hP1R-WT. The most potent analog, [Ala(3,10,12),Arg(11), Trp(14)]rPTH(1-14)NH(2), stimulated inositol phosphate production with hP1R-WT. The results show that short NH(2)-terminal peptides of PTH can be optimized for considerable gains in signaling potency through modification of interactions involving the regions of the receptor containing the transmembrane domains and extracellular loops.

Animals↗
PubMed1993

Effect of thyroxine on testicular function, circulating luteinising hormone and pituitary sensitivity to luteinising hormone-releasing hormone in the cockerel (Gallus domesticus).

1. The effect of thyroxine (T4) on reproductive function in the adult cockerel was followed for 11 weeks. Broiler cockerels aged 96 weeks were fed on diets containing either 0, 2 or 5 mg T4/kg for 4 weeks. 2. Daily sperm output (DSO) was significantly reduced (P < 0.01) in the T4-treated groups compared with that of controls at weeks 5 and 7. In the group given 5 mg T4/kg, plasma testosterone concentration was significantly reduced (P < 0.01) compared with that in controls during the T4 treatment, in spite of the fact that there was a decrease in concentration in both control and experimental birds. Plasma luteinising hormone (LH) concentration was significantly decreased (P < 0.05) in both of the groups given T4 treatments after 3 weeks. 3. Plasma testosterone concentrations and DSO had returned to control values at weeks 5 and 11 respectively, while plasma LH showed a transient but significant (P < 0.001) rebound after removal of thyroxine from the food. 4. In contrast to other variables, the pituitary responsivity to cLHRH-I injections, was not decreased during the feeding of the T4 diet but was, on the contrary, significantly increased (P < 0.05) during treatment with 5 mg T4/kg diet, and after the end of the treatment with 2 mg T4/kg diet. 5. These results provide some evidence for an inhibitory effect of large doses of T4 on the reproductive function in the adult cockerel. Although the possibility of a direct effect of T4 on the testes cannot be excluded, T4 is likely to act, at least in part, at the hypothalamo-pituitary level, and not through a reduction in the pituitary sensitivity to LHRH.

Animals↗
PubMed1994

Effects of gonadal steroids on tonic luteinizing hormone (LH) release and luteinizing hormone-releasing hormone-induced LH release from bovine pituitary cells cultured in vitro.

The objective of this study was to investigate the direct effect of estradiol-17 beta (E2) and progesterone (P4) on LH release by pituitary cells of midluteal phase cows in vitro. Pituitaries were collected at the slaughterhouse; cells were dissociated with collagenase and hyaluronidase and maintained in a static culture system in Medium 199 (M199). Various concentrations of E2 (0.1-100 nM) and P4 (0.1 and 10 nM) were used to stimulate the cells for 2, 4, 6, 15, 24, 48, or 72 h. In addition, the synergistic action of E2 and P4 was investigated by exposure of the cells to a combination of the two hormones. At the end of each incubation, the cells were challenged with LHRH (1 nM) for 2 h. The medium was collected for LH analysis at the end of each incubation period and after the LHRH challenge; furthermore, intracellular LH content was quantified at the end of each experiment. The results indicate a positive action of E2 on basal release of LH beginning after 15 h of exposure (p < 0.01). LHRH-induced LH release was modulated by E2 in a time-dependent manner with an effect at first inhibitory, then stimulatory, and finally inhibitory again (p < 0.04). P4 alone did not affect LH release, but it negatively influenced LHRH-induced LH release. P4 also exerted a positive action on intracellular LH after 6 h of incubation. A substantial inhibitory effect (p < 0.001) on both tonic LH release and LHRH-induced LH release was observed in cells exposed for 16 h to P4 after a priming with E2 for 4 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

A controlled trial of methionyl growth hormone therapy in prepubertal children with short stature, subnormal growth rate and normal growth hormone response to secretagogues. Dutch Growth Hormone Working Group.

Thirty short and slowly growing children with normal plasma growth hormone (GH) responses to standard provocation tests were randomly assigned to either a group (n = 20) undergoing treatment with methionyl GH (somatrem), 2 IU per m2 body surface s.c. daily, or a control group (n = 10). Twelve out of 18 children who completed the first year of treatment showed a height velocity increment of more than 2 cm/year. The mean (SD) growth velocity of the treatment group increased by 3.0 (1.9) cm/year over the first year, compared with -0.2 (0.7) cm/year in the control group. Neither parameters of endogenous GH secretion nor plasma IGF-I levels showed a significant correlation with the growth response. Of the auxological variables studied, pre-treatment growth velocity (r = -0.8) and the short-term height velocity increment (r = 0.7-0.9) showed significant correlations with the growth response in the first year of treatment. Somatrem therapy was without side effects, except in one child who developed anti-GH antibodies in combination with a poor growth response.

Body Height↗
PubMed1991

Chronic growth hormone administration does not suppress endogenous growth hormone secretion in patients with neurosecretory growth hormone dysfunction.

Short children who respond normally to growth hormone (GH) stimulation, but have a subnormal spontaneous secretion of GH (neurosecretory GH dysfunction, NSD) are treated with exogenous GH which might suppress their endogenous GH secretion. The effect of chronic administration of GH (8-24 months) on plasma GH responses to GHRH, clonidine and spontaneous GH secretion were studied in 17 NSD patients. The diagnosis of NSD was based on a normal GH response to clonidine (greater than 10 micrograms/l) and an integrated concentration of (IC-GH) GH less than 3.2 micrograms/l. The GH dose used in this study was 0.25 IU/kg three times a week in 10 patients and 0.05 IU/kg daily in 7 patients. Insulin-like growth factor I levels (nmol) increased significantly on therapy from 9.3 +/- 3.8 to 24.4 +/- 22.4 (p less than 0.001). The GH response (microgram/l) to GHRH was 20.4 +/- 5.5 before treatment and 22.4 +/- 6.2 on GH. Peak GH after clonidine was 22.4 +/- 8.9 and 22.8 +/- 8.1, respectively. There was no significant decrease in the number of GH spontaneous peaks (1.8 +/- 0.7 vs. 2.0 +/- 0.7, respectively) or in the area under the curve. A subcutaneous GH bolus of 0.25 IU/kg in 4 patients resulted in a GH peak of 55-82 micrograms/l at 3-5 h and a gradual return to basal levels at 15-20 h after GH administration. The first spontaneous GH peak appeared 26-28 h after GH injection, peak amplitude was 10-15 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Determination by Skeleton↗
PubMed2003

Central administration of neuropeptide Y reduces alpha-melanocyte-stimulating hormone-induced cyclic adenosine 5'-monophosphate response element binding protein (CREB) phosphorylation in pro-thyrotropin-releasing hormone neurons and increases CREB phosphorylation in corticotropin-releasing hormone neurons in the hypothalamic paraventricular nucleus.

Neuropeptide Y (NPY) has a potent inhibitory effect on TRH gene expression in the paraventricular nucleus (PVN) and contributes to the fall in circulating thyroid hormone levels during fasting mediated by a reduction in serum leptin levels. Because alpha-MSH activates the TRH gene by increasing the phosphorylation of CREB in the nucleus of these neurons, we raised the possibility that at least one of the mechanisms by which NPY reduces TRH mRNA in hypophysiotropic neurons is by antagonizing the ability of alpha-MSH to phosphorylate CREB. As NPY increases CRH mRNA in the hypothalamus, we further determined whether intracerebroventricular (i.c.v.) administration of NPY regulates the phosphorylation of CREB in hypophysiotropic CRH neurons. NPY [10 micro g in artificial CSF (aCSF)] was administered into the lateral ventricle i.c.v. 30 min before the i.c.v. administration of aCSF or alpha-MSH (10 micro g in aCSF), the latter in a dose previously demonstrated to increase proTRH mRNA and phosphorylate CREB in TRH neurons. By double-labeling immunocytochemistry, only few TRH neurons in the PVN contained phosphoCREB (PCREB) in animals treated only with aCSF (4 +/- 0.2%) or with NPY followed by aCSF (9.7 +/- 2.5), whereas alpha-MSH-infused animals dramatically increased the percentage of TRH neurons containing PCREB (75.3 +/- 6.9%). Pretreatment with NPY before alpha-MSH infusion, however, significantly reduced the percentage of TRH neurons containing PCREB (40.8 +/- 3.5%) compared with alpha-MSH infused animals (P = 0.01). Only 12.2 +/- 0.9% of CRH neurons of the medial parvocellular neurons contained PCREB nuclei in vehicle-treated animals, whereas 30 min following NPY infusion, the number of CRH neurons containing PCREB increased dramatically to 88 +/- 2.9%. Whereas alpha-MSH infusion increased the percentage of CRH neurons that contained PCREB to 56 +/- 2.2% compared with control, animals pretreated with NPY further increased the number of CRH neurons colocalizing with PCREB to 87 +/- 2.5%. These data demonstrate a functional interaction between NPY and alpha-MSH in the regulation of proTRH neurons in the PVN, suggesting that NPY can antagonize alpha-MSH induced activation of the TRH gene by interfering with melanocortin signaling at the postreceptor level, preventing the phosphorylation of CREB. In contrast, NPY infusion increases the phosphorylation of CREB in CRH neurons, indicating that NPY has independent effects on discrete populations of neurons in the PVN, presumably mediated through different signaling mechanisms.

Animals↗
PubMed2006

Identification of the chicken growth hormone-releasing hormone receptor (GHRH-R) mRNA and gene: regulation of anterior pituitary GHRH-R mRNA levels by homologous and heterologous hormones.

GHRH stimulates GH secretion in chickens as in mammals. However, nothing is known about the chicken GHRH receptor (GHRH-R). Here we report the cDNA sequence of chicken GHRH-R. Comparison of the cDNA sequence with the chicken genome localized the GHRH-R gene to chicken chromosome 2 and indicated that the chicken GHRH-R gene consists of 13 exons. Expression of all exons was confirmed by RT-PCR amplification of pituitary mRNA. The amino acid sequence predicted by the GHRH-R cDNA is homologous to that in other vertebrates and contains seven transmembrane domains and a conserved hormone-binding domain. The predicted size of the GHRH-R protein (48.9 kDa) was confirmed by binding of (125)I-GHRH to chicken pituitary membranes and SDS-PAGE. GHRH-R mRNA was readily detected by RT-PCR in the pituitary but not in the hypothalamus, total brain, lung, adrenal, ovary, or pineal gland. Effects of corticosterone (CORT), GHRH, ghrelin, pituitary adenylate cyclase-activating peptide, somatostatin (SRIF), and TRH on GHRH-R and GH gene expression were determined in cultures of chicken anterior pituitary cells. GHRH-R and GH mRNA levels were determined by quantitative real-time RT-PCR. Whereas all treatments affected levels of GH mRNA, only CORT, GHRH, and SRIF significantly altered GHRH-R mRNA levels. GHRH-R gene expression was modestly increased by GHRH and suppressed by SRIF at 4 h, and CORT dramatically decreased levels of GHRH-R mRNA at 72 h. We conclude that adrenal glucocorticoids may substantially impact pituitary GH responses to GHRH in the chicken through modulation of GHRH-R gene expression.

Amino Acid Sequence↗
PubMed1981

In vitro effect of danazol on luteinizing hormone-releasing hormone-stimulated luteinizing hormone release in rat anterior pituitary cell cultures in vitro.

Monolayer cultures of anterior pituitary glands from female rats were exposed to 5 X 10(-6) M danazol for 0, 4, 24, 48, and 72 h in Dulbecco's Modified Eagle's Medium supplemented with 10% horse serum and 2.5% fetal calf serum. After this treatment, the cell cultures were rinsed and challenged with 10(-8) M LHRH for 6 h. The media were collected and assayed for LH by a hormone-specific RIA using the double antibody precipitation technique. A control incubation was carried out by exposing cell cultures for the same length of time in the absence of danazol but in the presence of 0.5% ethanol in which danazol was dissolved, then challenging the culture with 10(-8) M LHRH, as was done in the experimental group, and assaying the LH released in the medium. The results showed that exposure of cell cultures to danazol caused a significant decrease in LH release in response to LHRH from 13,800 +/- 500 to 3,500 +/- 200 ng/ml. The inhibition of LH release was dependent on both the duration of danazol exposure and its concentration. Danazol exposure had, however, little effect on basal LH secretion by the pituitaries, which remained at about 600 ng/ml at all time points examined. Under the experimental conditions, danazol exerted no effect on the incorporation of amino acid into protein in the cell culture. These results suggest that one of the mechanisms of the antigonadotropic effect of danazol is inhibition of the responsiveness of the pituitary to LHRH-induced LH release.

Animals↗
PubMed1982

Simultaneous measurement of luteinizing hormone-releasing hormone and luteinizing hormone release in unanesthetized, ovariectomized sheep.

The push-pull perfusion technique was used in combination with a sequential bleeding schedule to estimate simultaneously the release patterns of LHRH and LH in unanesthetized ovariectomized sheep and to determine the temporal relationship between the release of these two hormones. Ovariectomized (greater than 30 days) ewes received unilateral push-pull cannula (PPC) implants (od, 0.85 mm) into the median eminence. After at least 6 days of recovery, each ewe was fitted with an indwelling jugular catheter. For push-pull perfusion, a stylette was removed from the outer PPC, and an inner cannula assembly (od, 0.40 mm) was inserted. Artificial cerebrospinal fluid was pushed through the inner cannula and pulled up between the cannulae at 20 microliters/min. Continuous 10-min perfusate fractions were collected, acidified, and stored at -20 C for LHRH RIA. Blood samples were obtained every 10 min via the jugular catheter, each being drawn 5 min after the start of a perfusate collection interval. Plasma LH levels were determined by RIA. The duration of the sampling was 3-7 h. LHRH output was distinctly pulsatile, occurring at a frequency of approximately one pulse every 30-40 min (n = 5 sheep). LHRH pulse amplitude and frequency remained relatively constant throughout each perfusion. Plasma LH values also were pulsatile, and all LH peaks occurred either during the same interval or during the interval after a LHRH pulse. LH pulses always were accompanied or directly preceded by LHRH pulses, but LHRH pulses were not always followed by LH pulses. The amplitudes of LH pulses and corresponding LHRH pulses were highly correlated (r = 0.81; P less than 0.01). Histological examination revealed that detection of LHRH in perfusates depended upon the placement of the PPC tip into either the zona externa of the central median eminence or adjacent areas. These experiments demonstrate that 1) hypothalamic LHRH release in the Ovx ewe occurs in discrete pulses, with a mean interpulse interval of 38.7 +/- 1.5 min, 2) LH pulses invariably are preceded or accompanied by LHRH pulses, and 3) LH pulse amplitude is highly correlated with LHRH pulse amplitude.

Animals↗
PubMed1985

Effects of ovarian hormones on the concentrations of immunoreactive neuropeptide Y in discrete brain regions of the female rat: correlation with serum luteinizing hormone (LH) and median eminence LH-releasing hormone.

Recent pharmacological studies have suggested a role for neuropeptide Y (NPY) in control of LH secretion. The present study examined the effects of estradiol benzoate (EB) given alone or in combination with progesterone (P), on the concentrations of immunoreactive NPY in microdissected nuclei of the rat brain, in association with changes in LHRH concentrations and LH release. Forty-eight hours after the administration of EB to ovariectomized rats, serum LH was significantly reduced. Concentrations of NPY, measured by a sensitive and specific RIA, were also reduced in the median eminence, arcuate nucleus, and interstitial nucleus of the stria terminalis. As expected, administration of P to these EB-primed rats induced a sequential rise and fall of LHRH in the median eminence, followed by a marked LH surge in the afternoon. Interestingly, NPY concentrations in the median eminence also increased and then decreased after P, with a time course similar to that shown by LHRH. In the arcuate nucleus and interstitial nucleus of the stria terminalis, P treatment did not affect NPY concentrations further. Sequential EB plus P treatment significantly reduced NPY levels in the medial preoptic nucleus compared to oil vehicle controls. Levels of immunoreactive NPY in the ventromedial nucleus and periventricular nucleus were largely unaffected by ovarian hormone treatments. These results indicate that ovarian steroids, which modulate LH secretion, affect NPY concentrations in those specific areas of the brain which are known to be innervated by the LHRH neurons. These observations support the hypothesis that NPY may participate in the neural regulation of LHRH and LH secretion.

Animals↗
PubMed1976

Inhibition of luteinizing hormone release by analogs of luteinizing hormone-releasing hormone (LHRH) in vitro.

Sixteen synthetic analogs of LH-releasing hormone (LHRH) were tested for their ability to inhibit the stimulation of LH release induced by 3 X 10(-9)M LHRH in anterior pituitary cells in monolayer culture. Half-maximal inhibition of LHRH-induced LH release was obtained with 7 analogs at concentrations which ranged from 3 X 10(-6)M to 3 X 10(-5)M. None of these seven analogs had significant LH-releasing activity at concentrations up to 10-5M. Nine analogs had no detectable antagonistic activity when tested in up to a 3000-fold molar ratio of analog to LHRH.

Animals↗
PubMed1976

Simulation of the early phase of the proestrous follicle-stimulating hormone rise after infusion of luteinizing hormone-releasing hormone in phenobarbital-blocked rats.

Four-day cycling rats were kept in a room with the lights on from 0500-1900 h. Plasma FSH concentrations in blood withdrawn through atrial cannulas at hourly intervals from 1400-2000 h on proestrus were very similar to serum FSH concentrations in blood collected by decapitation. Additional cannulated rats were bled at 20 min intervals from 1400-1600, 1600-1800, or 1800-2000 h. In most rats, plasma FSH concentration rose gradually to approximately three times pre-rise levels by 1900 h. It then decreased slightly by 2000 h. Injection of an ovulation-blocking dosage of phenobarbital at 1345 h blocked the FSH rise. Rapid injection of 124 or 1240 ng of LHRH at 1300 h did not elevate plasma FSH by 1315 h but the 1240 ng dose did by 1400 h. Phenobarbital injection at 1230 h did not alter this response. In additional blocked rats, blood was rapidly withdrawen through one of two indwelling atrial cannulas while LHRH was infused at a constant rate through the other. Administration of LHRH by infusion was much more effective in elevating plasma FSH than was rapid injection of the releasing hormone. The pattern of plasma FSH concentration after infusion of about 50 ng of LHRH per hour from 1500-1810 h and then about 12 ng of LHRH per hour from 1810-1920 h was remarkably similar to that of the spontaneous FSH rise. These experiments imply that the early phase of the FSH surge (the one associated with the proestrous LH surge) is caused by a properly timed, nearly constant-rate release of LHRH for about 3 h (beginning about 1500 h of proestrus) followed by a period of diminished LHRH release.

Animals↗
PubMed1996

Regulation of hypothalamic somatostatin, growth hormone-releasing hormone, and growth hormone receptor messenger ribonucleic acid by glucocorticoids.

Although it is well known that chronic treatment with glucocorticoids inhibits somatic growth, the mechanism of action of this inhibitory effect is not completely understood. It is likely that glucocorticoids act at various levels, including pituitary, hypothalamus, and peripheral organs modulating GH synthesis, secretion, and action. In this work, we evaluated the effect of dexamethasone on hypothalamic somatostatin and GH-releasing hormone (GHRH) messenger RNA (mRNA) levels by in situ hybridization. We found a significant decrease of somatostatin mRNA content in the periventricular nucleus of the hypothalamus after 3, 8, and 15 days of treatment with dexamethasone. Furthermore, we observed a reduction in GHRH mRNA levels in the arcuate nucleus after 8 and 15 days of treatment with this steroid. As it has been shown that GH feeds back to regulate somatostatin and GHRH expression at the hypothalamic level through high affinity GH receptors, we evaluated the possibility of a GH-mediated action in the inhibitory effect of glucocorticoids on somatostatin and GHRH mRNA levels. To address this issue, we first studied the GH receptor mRNA content in both the periventricular and arcuate nuclei of the hypothalamus after dexamethasone treatment. Secondly, the effect of dexamethasone on somatostatin and GHRH mRNA levels in hypophysectomized animals also was assessed. We found a significant decrease in GH receptor mRNA levels in the periventricular nucleus and in the arcuate nucleus after 1, 3, 8, and 15 days of glucocorticoid administration. Finally, in hypophysectomized rats, dexamethasone treatment for 15 days did not reduce somatostatin mRNA levels in the periventricular nucleus but significantly decreased GHRH mRNA content in the arcuate nucleus. In summary, our results suggest an inhibitory GH-mediated effect of dexamethasone on somatostatin mRNA levels in the periventricular nucleus and an inhibitory direct effect of dexamethasone on GHRH neurones in the arcuate nucleus.

Animals↗