scholarly journals Severe uremia depresses the ability of perifused rat pituitary cells to secrete growth hormone in response to growth hormone releasing hormone.

1997 ◽  
Vol 8 (5) ◽  
pp. 742-748
Author(s):  
J Rodríguez ◽  
F Santos ◽  
M J García de Boto ◽  
E García ◽  
V Martínez ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Dose Response ◽  
Secretory Response ◽  
Pituitary Cells ◽  
Maximal Effect ◽  
Response Curves ◽  
Secretory Rate ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Dose Response Curves

To examine whether growth hormone (GH) secretion is impaired by chronic renal failure (CRF) and to gain some insight into the influence of uremia itself and associated malnutrition, the GH secretory response of dispersed anterior pituitary cells perifused with GH-releasing hormone (GHRH) was investigated in 5/6 nephrectomized (UREM, N = 15) and three groups (N = 15 each) of normal renal function, sham-operated rats under three different nutritional conditions: fed "ad libitum" (SAL), pair-fed with a diet similar to the UREM group (SPF), and pair-fed with a diet similar to the UREM group in terms of protein ingestion but calorically supplemented up to intake of SAL group (SPF+). Ten days after nephrectomy, UREM rats had severe CRF, as shown by much higher (P < 0.0001) serum urea nitrogen concentrations (X +/- mean +/- SE) than sham groups (59 +/- 6 versus 8 +/- 0, 9 +/- 0, and 5 +/- 0 mmol/L, respectively), and they were growth retarded, as shown by lower gains (P < 0.0001) in weight (13.5 +/- 2.5 versus 62 +/- 2.1, 20.5 +/- 1.9, and 50.4 +/- 1.0 g) and length (2.9 +/- 0.2 versus 5.8 +/- 0.1, 3.6 +/- 0.1, and 5.6 +/- 0.1 cm). Perifusion studies showed similar basal GH secretory rate (ng/min/10(7) cells) in the four groups. A fixed sequence of progressively increasing GHRH doses resulted in a lower overall mean GH secretion in UREM rats (15.8 +/- 1.6 ng/min/10(7) cells), as compared with SAL (50.8 +/- 9.0 ng/min/10(7) cells, P < 0.01), SPF (33.0 +/- 3.3 ng/min/10(7) cells, P < 0.05), and SPF+ (49.4 +/- 5.1 ng/min/10(7) cells, P < 0.01) groups. Analysis of dose-response curves showed that the maximal secretory response was produced by the same concentration of GHRH (10 nM) in the four groups and was lower (P < 0.01) in UREM than SAL and SPF+ rats (34.9 +/- 5.0 versus 115.7 +/- 28.4 and 98.9 +/- 9.8 ng/min/10(7) cells). The concentration of GHRH that caused the half of maximal effect was identical, close to 1 nM, in the four groups of animals. This study provides direct evidence that the ability of pituitary cells to secrete GH in response to GHRH is depressed in severe CRF. The lower secretory capacity of pituitary gland is only partly dependent on caloric malnutrition associated with CRF. Data of dose-response curves suggest that decreased GH secretion may be related to a lesser number of pituitary receptors for GHRH.

scholarly journals Restoration of Susceptibility of Intracellular Methicillin-Resistant Staphylococcus aureus to β-Lactams: Comparison of Strains, Cells, and Antibiotics

2008 ◽  
Vol 52 (8) ◽  
pp. 2797-2805 ◽  
Author(s):  
Sandrine Lemaire ◽  
Aurélie Olivier ◽  
Françoise Van Bambeke ◽  
Paul M. Tulkens ◽  
Peter C. Appelbaum ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Dose Response ◽  
Intermediate Phenotype ◽  
Maximal Effect ◽  
Response Curves ◽  
Methicillin Resistant ◽  
Complete Restoration ◽  
Similar Dose ◽  
Dose Response Curves ◽  
Mrsa Strains

ABSTRACT Staphylococcus aureus invades eukaryotic cells. When methicillin-resistant S. aureus (MRSA) ATCC 33591 is phagocytized by human THP-1 macrophages, complete restoration of susceptibility to cloxacillin and meropenem is shown and the strain becomes indistinguishable from MSSA ATCC 25923 due to the acid pH prevailing in phagolysosomes (S. Lemaire et al., Antimicrob. Agents Chemother. 51:1627-1632, 2007). We examined whether this observation can be extended to (i) strains of current clinical and epidemiological interest (three hospital-acquired MRSA [HA-MRSA] strains, two community-acquired MRSA [CA-MRSA] strains, two HA-MRSA strains with the vancomycin-intermediate phenotype, one HA-MRSA strain with the vancomycin-resistant phenotype, and one animal [porcine] MRSA strain), (ii) activated THP-1 cells and nonprofessional phagocytes (keratinocytes, Calu-3 bronchial epithelial cells), and (iii) other β-lactams (imipenem, oxacillin, cefuroxime, cefepime). All strains showed (i) a marked reduction in MICs in broth at pH 5.5 compared with the MIC at pH 7.4 and (ii) sigmoidal dose-response curves with cloxacillin (0.01× to 100× MIC, 24 h of incubation) after phagocytosis by THP-1 macrophages that were indistinguishable from each other and from the dose-response curve for methicillin-susceptible S. aureus (MSSA) ATCC 25923 (relative potency [50% effect], 6.09× MIC [95% confidence interval {CI}, 4.50 to 8.25]; relative efficacy [change in bacterial counts over the original inoculum for an infinitely large cloxacillin concentration, or maximal effect], −0.69 log CFU [95% CI, −0.79 to −0.58]). Similar dose-response curves for cloxacillin were also observed with MSSA ATCC 25923 and MRSA ATCC 33591 after phagocytosis by activated THP-1 macrophages, keratinocytes, and Calu-3 cells. By contrast, there was a lower level of restoration of susceptibility of MRSA ATCC 33591 to cefuroxime and cefepime after phagocytosis by THP-1 macrophages, even when the data were normalized for differences in MICs. We conclude that the restoration of MRSA susceptibility to β-lactams after phagocytosis is independent of the strain and the types of cells but varies between β-lactams.

scholarly journals Regulation of gonadotrophin secretion by inhibin, testosterone and gonadotrophin-releasing hormone in pituitary cell cultures of male monkeys

1998 ◽  
Vol 159 (1) ◽  
pp. 103-110 ◽  
Author(s):  
U Fingscheidt ◽  
GF Weinbauer ◽  
HL Fehm ◽  
E Nieschlag
Keyword(s):  
Dose Response ◽  
Pituitary Cells ◽  
Basal Secretion ◽  
Response Curves ◽  
Gonadotrophin Secretion ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone ◽  
Dose Response Curves ◽  
Male Rhesus

The effects of bovine inhibin, testosterone and GnRH on gonadotrophin secretion by primate pituitary cells were characterized in vitro using pituitaries from six male rhesus monkeys and one male cynomolgus monkey. The effect of inhibin on basal secretion of FSH and LH was investigated. Dose-response curves in monkeys and rats were compared. GnRH dose-response curves in the presence and absence of testosterone were also examined in monkeys. In monkey pituitary cells, testosterone at a concentration of 10(-7) M had no effect on LH or FSH secretion. Inhibin suppressed FSH secretion to 50.8% of that of controls with no effect on LH. In rats, FSH secretion was suppressed to 45.0% of that of controls with a median effective dose (ED50, 95% range) of 1.298 (1.064-1.584) U/ml, compared with 1.024 (0.7204-1.455) U/ml in monkeys. In monkey pituitary cells, LH release was stimulated 9.9-fold and FSH 3.3-fold by GnRH. Testosterone had no effect on basal or GnRH-stimulated gonadotrophin release. These results support the view that the pituitary is not the target organ for the negative feedback action of testosterone in the male. In vitro, inhibin is the major regulator of FSH secretion at the pituitary level.

Neuropeptide Y directly inhibits growth hormone secretion by human pituitary somatotropic tumours

1987 ◽  
Vol 115 (1) ◽  
pp. 149-154 ◽  
Author(s):  
Eric F. Adams ◽  
Maria S. Venetikou ◽  
Christine A. Woods ◽  
S. Lacoumenta ◽  
J. M. Burrin
Keyword(s):  
Growth Hormone ◽  
Neuropeptide Y ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Inhibitory Effect ◽  
Pituitary Cells ◽  
Maximal Effect ◽  
Human Pituitary ◽  
Amino Acid Peptide ◽  
Gh Secretion

Abstract. Neuropeptide Y (NPY) is a 36 amino acid peptide, widely distributed throughout the brain and is found in hypothalamic neurones. This latter finding suggests that NPY may possess a hypophysiotropic function. A number of studies have demonstrated effects of NPY on LH and GH secretion by rat pituitary cells. We report here the results of experiments investigating the effects of NPY on GH secretion by tumorous human somatotropic pituitary cells in culture. NPY (0.25–25 nmol/l) inhibited GH secretion by 20–53%, the maximal effect depending upon the tumour studied. The potency of NPY was less than that of somatostatin (SRIH). The stimulatory effects of growth hormone releasing factor (GHRH) and theophylline were reduced by NPY, but NPY did not modify the inhibitory effect of SRIH on GH secretion. It is concluded that NPY may be involved in the control of GH secretion, at least by tumorous human pituitary somatotropes.

scholarly journals A Rapid, Sensitive and Reliable Assay for Inhibin Bioactivity

1987 ◽  
Vol 40 (1) ◽  
pp. 105 ◽  
Author(s):  
V WK Lee ◽  
Noelene Colvin ◽  
Helen Quigg ◽  
Lynne Atley ◽  
Julie McMaster ◽  
...  
Keyword(s):  
Dose Response ◽  
Culture Media ◽  
Rete Testis ◽  
Female Rats ◽  
Pituitary Cells ◽  
Response Curves ◽  
Cell Content ◽  
Practical Capacity ◽  
Pituitary Glands ◽  
Dose Response Curves

A rapid 2-day quantitative assay for inhibin bioactivity based on FSH secretion from pituitary cells of immature female rats is described. The bioassay exhibited steeper slopes, improved precision and greater (fourfold) sensitivity compared with a previously established pituitary FSH cell content assay. Whole pituitary glands were used for the preparation of pituitary cells and the method for cell dispersion required a single enzymatic treatment with trypsin. Cells (180000 viable cells per well) were dispensed into culture media containing inhibin and incubated for 48 h. Media were removed and assayed for FSH by radioimmunoassay. Using a ram rete testis fluid preparation as standard the inhibin dose-response curves of 25 consecutive experiments showed indices of precision of - O� 08(mean)[range - 0�04 to - 0�17] and Finney's G values of 0�017[0�003-0�06]. The mean ED40 was 0�17 units of in hi bin activity per well with interassay variation of 16�2% at this point of the dose-response curve. The assay had a practical capacity of 400 wells, permitting the measurement of dose-response curves of at least 40 unknowns with three dose points and triplicate wells per dose. The assay is specific for inhibin-containing preparations from several animal species. Overall, the assay is simple, precise, and sensitive, indicative of its applicability to the measurement of inhibin samples with low inhibin bioactivity and to the screening of large numbers of fractions during inhibin purification.

PKC and ERK are differentially involved in gonadotropin-releasing hormone-induced growth hormone gene expression in the goldfish pituitary

2005 ◽  
Vol 289 (6) ◽  
pp. R1625-R1633 ◽  
Author(s):  
Christian Klausen ◽  
Takeshi Tsuchiya ◽  
John P. Chang ◽  
Hamid R. Habibi
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Primary Cultures ◽  
Gonadotropin Releasing Hormone ◽  
Growth Hormone Gene ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Gh Gene

Gonadotropin-releasing hormone (GnRH) is produced by the hypothalamus and stimulates the synthesis and secretion of gonadotropin hormones. In addition, GnRH also stimulates the production and secretion of growth hormone (GH) in some fish species and in humans with certain clinical disorders. In the goldfish pituitary, GH secretion and gene expression are regulated by two endogenous forms of GnRH known as salmon GnRH and chicken GnRH-II. It is well established that PKC mediates GnRH-stimulated GH secretion in the goldfish pituitary. In contrast, the signal transduction of GnRH-induced GH gene expression has not been elucidated in any model system. In this study, we demonstrate, for the first time, the presence of novel and atypical PKC isoforms in the pituitary of a fish. Moreover, our results indicate that conventional PKCα is present selectively in GH-producing cells. Treatment of primary cultures of dispersed goldfish pituitary cells with PKC activators (phorbol ester or diacylglycerol analog) did not affect basal or GnRH-induced GH mRNA levels, and two different inhibitors of PKC (calphostin C and GF109203X) did not reduce the effects of GnRH on GH gene expression. Together, these results suggest that, in contrast to secretion, conventional and novel PKCs are not involved in GnRH-stimulated increases in GH mRNA levels in the goldfish pituitary. Instead, PD98059 inhibited GnRH-induced GH gene expression, suggesting that the ERK signaling pathway is involved. The results presented here provide novel insights into the functional specificity of GnRH-induced signaling and the regulation of GH gene expression.

Mechanisms for gonadotropin-releasing hormone potentiation of growth hormone rebound following norepinephrine inhibition in goldfish pituitary cells

2007 ◽  
Vol 292 (1) ◽  
pp. E203-E214 ◽  
Author(s):  
Anderson O. L. Wong ◽  
Maggie C. Y. Chuk ◽  
Hiu Chi Chan ◽  
Eric K. Y. Lee
Keyword(s):  
Growth Hormone ◽  
Adrenergic Receptors ◽  
Gonadotropin Releasing Hormone ◽  
Pituitary Cells ◽  
Adrenergic Stimulation ◽  
Dependent Protein Kinase ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Dependent Protein ◽  
Subsequent Activation

In the goldfish, norepinephrine (NE) inhibits growth hormone (GH) secretion through activation of pituitary α2-adrenergic receptors. Interestingly, a GH rebound is observed after NE withdrawal, which can be markedly enhanced by prior exposure to gonadotropin-releasing hormone (GnRH). Here we examined the mechanisms responsible for GnRH potentiation of this “postinhibition” GH rebound. In goldfish pituitary cells, α2-adrenergic stimulation suppressed both basal and GnRH-induced GH mRNA expression, suggesting that a rise in GH synthesis induced by GnRH did not contribute to its potentiating effect. Using a column perifusion approach, GnRH given during NE treatment consistently enhanced the GH rebound following NE withdrawal. This potentiating effect was mimicked by activation of PKC and adenylate cyclase (AC) but not by induction of Ca2+ entry through voltage-sensitive Ca2+ channels (VSCC). Furthermore, GnRH-potentiated GH rebound could be alleviated by inactivation of PKC, removal of extracellular Ca2+, blockade of VSCC, and inhibition of Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). Inactivation of AC and PKA, however, was not effective in this regard. These results, as a whole, suggest that GnRH potentiation of GH rebound following NE inhibition is mediated by PKC coupled to Ca2+ entry through VSCC and subsequent activation of CaMKII. Apparently, the Ca2+-dependent cascades are involved in GH secretion during the rebound phase but are not essential for the initiation of GnRH potentiation. Since GnRH has been previously shown to have no effects on cAMP synthesis in goldfish pituitary cells, the involvement of cAMP-dependent mechanisms in GnRH potentiation is rather unlikely.

Maximal acid secretory response to histamine and its relation to parietal cell mass in the dog

1960 ◽  
Vol 199 (3) ◽  
pp. 579-588 ◽  
Author(s):  
I. N. Marks ◽  
S. A. Komarov ◽  
Harry Shay
Keyword(s):  
Dose Response ◽  
Acid Output ◽  
Cell Mass ◽  
Parietal Cells ◽  
Secretory Response ◽  
Response Curves ◽  
Entire Duration ◽  
The Mean ◽  
Dose Response Curves ◽  
Histamine Response

Gastric secretion in response to graded doses of histamine was obtained from the whole stomach in five trained dogs, and the animals were sacrificed to determine the total number of parietal cells in the stomach. Histamine was administered by single s.c. injection (Hsc) and continuous i.v. infusion (Hiv). Maximal histamine response (MHR) was determined, and studies permitting the construction of dose-response curves were carried out in three of the five dogs. Dose-response curves for acidity and for acid output and volume during the entire duration of secretory response to Hsc were also established. The MHR was found to be a linear function of both the total number of parietal cells ( P < .01) and the fundic mucosal volume ( P < .05). The magnitude of the MHR and the PCM in the five dogs was within the respective ranges reported in man, but the mean MHR per billion cells (9.8 ± 0.44 mEq/30 min.) and the mean MHR per 100 cc fundic mucosal volume (58.2 ± 5.12 mEq/30 min.) were both about 30% less than the respective ratios in man.

Sign in / Sign up

Export Citation Format

Share Document