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Biomedical subjects

G Pelletier

Publications and source records attributed to G Pelletier.

At least 361 records · Page 20Linked to original sources

Regulation of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase expression and activity in the hypophysectomized rat ovary: interactions between the stimulatory effect of human chorionic gonadotropin and the luteolytic effect of prolactin.

The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) catalyzes an obligatory step in the conversion of pregnenolone and other 5-ene-3 beta-hydroxysteroids into progesterone as well as precursors of all androgens and estrogens in the ovary. Since 3 beta-HSD is likely to be an important target for regulation by pituitary hormones, we have studied the effect of chronic treatment with LH (hCG), FSH, and PRL on ovarian 3 beta-HSD expression and activity in hypophysectomized adult female rats. Human CG (hCG) [10 IU, twice a day (bid)], ovine FSH (0.5 microgram, bid), and ovine PRL (1 mg, bid) were administered, singly or in combination, for a period of 10 days starting 15 days after hypophysectomy. In hypophysectomized rats, PRL exerted a potent inhibitory effect on all the parameters studied. In fact, PRL caused a 81% decrease in ovarian 3 beta-HSD mRNA content accompanied by a similar decrease in 3 beta-HSD activity and protein levels. In addition, ovarian weight decreased by 40% whereas serum progesterone fell dramatically from 1.92 nmol/liter to undetectable levels after treatment with PRL. Whereas hCG alone had only slight stimulatory effects on 3 beta-HSD mRNA, protein content and activity levels, treatment with the gonadotropin partially or completely reversed the potent inhibitory effects of oPRL on all the parameters measured. FSH, on the other hand, had no significant effect on 3 beta-HSD expression and activity. In situ hybridization experiments using the 35S-labeled rat ovary 3 beta-HSD cDNA probe show that the inhibitory effect of PRL is exerted primarily on luteal cell 3 beta-HSD expression and activity. On the other hand, it can be seen that hCG stimulates 3 beta-HSD mRNA accumulation in interstitial cells. The present data show that hCG and PRL exert potent and opposite cell-specific effects on ovarian 3 beta-HSD expression, activity, and content in the rat ovary. Moreover, the present study could suggest that female infertility associated with hyperprolactinemia in women could well be related, at least in part, to the potent inhibitory effect of PRL on ovarian 3 beta-HSD expression and activity.

3-Hydroxysteroid Dehydrogenases↗

Effect of long-term administration of porcine growth hormone-releasing factor and(or) thyrotropin-releasing factor on growth hormone, prolactin and thyroxine concentrations in growing pigs.

Long-term administration of porcine growth hormone-releasing factor (pGRF(1-29)NH2) and(or) thyrotropin-releasing factor (TRF) was evaluated on serum concentrations of growth hormone (GH) thyroxine (T4) and prolactin (PRL). Twenty-four 12-wk-old female Yorkshire-Landrace pigs were injected at 1000 and 1600 for 12 wk with either saline, pGRF (15 micrograms/kg), TRF (6 micrograms/kg) or pGRF + TRF using a 2 x 2 factorial design. Blood samples were collected on d 1, 29, 57 and 85 of treatment from 0400 to 2200. Areas under the GH, T4 and PRL curves (AUC) for the 6 h (0400 to 1000) prior to injection were subtracted from the postinjection periods (1000 to 1600, 1600 to 2200) to calculate the net hormonal response. The AUC of GH for the first 6 h decreased similarly (P less than .05) with age for all treatments. The GH response to GRF remained unchanged (P greater than .10) across age. TRF alone did not stimulate (P less than .05) GH release but acted in synergy with GRF to increase (P less than .05) GH release. TRF stimulated (P less than .001) the net response of T4 on all sampling days. Animals treated with the combination of GRF + TRF showed a decreased T4 AUC during the first 6 h on the last three sampling days. Basal PRL decreased (P less than .05) with age. Over the four sampling days, animals injected with TRF alone showed (P less than .01) a reduction (linear effect; P less than .01) followed by an increase (quadratic effect; P less than .05) in total PRL concentration after injection; however, when GRF was combined with TRF, such effects were not observed (P greater than .10). Results showed that 1) chronic injections of GRF for 12 wk sustained GH concentration, 2) TRF and GRF acted synergistically to elevate GH AUC, 3) TRF increased T4 concentrations throughout the 12-wk treatment period, 4) chronic TRF treatment decreased the basal PRL concentration and 5) chronic GRF + TRF treatment decreased the basal concentration of T4.

Animals↗

Effect of dose and frequency of administration of a potent analog of human growth hormone-releasing factor on hormone secretion and growth in pigs.

Ninety-six pigs (49.5 +/- .5 kg BW) were allotted to six treatments and were injected once (SID) or three times daily (TID) s.c. with a [desamino-Tyr1, D-Ala2, Ala15] human growth hormone-releasing factor (1-29) NH2 analog (GRF-AN). Treatments were T1, noninjected control; T2, saline-injected control (TID); T3, GRF-AN (1.66 micrograms/kg BW, TID); T4, GRF-AN (3.33 micrograms/kg BW, TID); T5, GRF-AN (6.66 micrograms/kg BW, TID) and T6, GRF-AN (10 micrograms/kg BW, SID). Feed protein levels were 14% for T1 and 18.8% for T2 through T6. The GRF-AN increased serum growth hormone (GH) concentration for the entire growing period (about 56 d) in a dose-related manner and did not induce desensitization of the somatotroph cells; in fact, an increase (P less than .05) in the GH response to GRF-AN was observed in T4 and T5 after 1 mo of treatment. This GRF-AN produced (P less than .05) a dose-dependent effect on several variables in animals grown to 110 kg BW: in comparison to T2, T5 increased meat in carcass (6%), carcass length (3%), loin eye area (13%), liver weight (19%), kidney weight (30%), improved feed efficiency (20%) and decreased total feed intake by 50 kg (26%). Compared to T2, average daily gain was increased (P less than .05) by 13% by the 3.33 micrograms/kg TID dose. Blood parameters were measured on d 1, 29 and 57. Increased serum glucose and insulin levels were observed. Triiodothyronine and thyroxine concentrations were increased and decreased, respectively after 28 d of treatment but were unchanged on d 57. This potent GRF analog maintained high GH concentration for at least 56 d and affected several growth parameters and carcass characteristics in a dose-related manner similar in magnitude to that reported in studies using porcine GH.

Animals↗

Effect of a potent analog of human growth hormone-releasing factor on carcass composition and quality of crossbred market pigs.

The effect of a human growth hormone-releasing factor (hGRF) analog ([desamino-Tyr1, D-Ala2, Ala15] hGRF(1-29)NH2) on the carcass composition of crossbred barrows was evaluated. pH, color and collagen content were measured on 74 animals distributed among the following five treatments started at about 50 kg BW: T1, control saline three times daily (TID); T2, hGRF analog (1.66 micrograms/kg, TID); T3, hGRF analog (3.33 micrograms/kg, TID); T4, hGRF analog (6.66 micrograms/kg, TID) and T5, hGRF analog (10 micrograms/kg, once daily). Animals were slaughtered at approximately 106 kg BW giving an average of 55 d on test. Carcass composition was determined on eight animals from T1 and eight animals from T4. The left side of each carcass was divided into four untrimmed commercial cuts: ham, loin, shoulder and belly, which then were dissected into muscle, separable fat, bone and skin. Ham, loin and belly weights were not affected by GRF treatment, but shoulder weight was increased (P less than .05; 10.11 vs 11.15 kg, SE = .21). There was an increase (P less than .0.05) in muscle content of all the cuts considered and a concomitant decrease (P less than .05) in fat content. The analog increased muscle weight by 16% and decreased fat weight by 25% in the pooled tissues of the shoulder, ham and loin. Overall, hGRF analog increased skin and bone weights by 39% and 19%, respectively. Chemical analysis demonstrated that the hGRF analog increased overall protein accretion in the carcass by 10.5% and decreased crude fat by 28.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Effect of human growth hormone-releasing factor and(or) thyrotropin-releasing factor on hormone concentrations in dairy calves.

To determine the effect of chronic treatment with human growth hormone-releasing factor (1-29)NH2 (GRF) and(or) thyrotropin-releasing factor (TRF), 20 calves averaging 70.2 kg BW were divided into four groups (n = 5) according to a 2 X 2 factorial design. For 86 d, calves in each group received twice daily s.c. injections of either .9% NaCl, GRF (5 micrograms/kg BW), TRF (1 microgram/kg BW) or GRF (5 micrograms/kg BW) plus TRF (1 microgram/kg BW). On d 87, all calves received a s.c. injection of GRF (5 micrograms/kg BW) plus TRF (1 microgram/kg BW). Blood samples were collected every 20 min for 18 h on d 1, 29, 57 and 85, and for 8 h on d 87. Hormone responses were measured as area under the hormone concentration curve over time. GRF and TRF acted in synergy (P less than .10) on GH release throughout the treatment period. Growth hormone responsiveness to GRF and(or) TRF decreased (P less than .01) with days of treatment, but this decrease was due to aging rather than to chronic treatment, because GH response to GRF plus TRF was similar (P greater than .10) between control and treated calves on d 87. TRF increased prolactin (Prl) concentration until the end of the treatment period (P less than .01). The response of thyroid-stimulating hormone (TSH) to TRF disappeared (P greater than .10) after 1 mo of treatment, whereas the thyroxine (T4) response decreased (P less than .01) throughout the treatment period. GRF did not induce nor did it interact with TRF on TSH and T4 release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Elective sclerotherapy in hepatocellular carcinoma complicated by digestive hemorrhage].

Between April 1984 and October 1988, 10 patients with hepatocellular carcinoma who bled from esophageal varices were included in a polidocanol sclerotherapy program, after the cessation of bleeding. Sixty cirrhotic patients without hepatocellular carcinoma were included as controls in the same sclerotherapy program for the same period. According to Okuda's classification, 1 patient was grade I, and 9 were grade II. At 1 year, 41 percent of patients with hepatocellular carcinoma and 51 percent of controls had rebled (non significant). Varices were obliterated in 7 of 10 patients with hepatocellular carcinoma and in 41 of 60 control patients (non significant). At one year, treatment failed (rebleeding or death) in 54 percent patients with hepatocellular carcinoma and in 59 percent control patients (non significant). Child-Pugh's score was the principal prognostic factor for treatment failure in both groups. Portal vein thrombosis was found in 2 of the 3 hepatocellular carcinoma patients who rebled. Unlike propranolol, elective sclerotherapy treatment might be proposed to patients with hepatocellular carcinoma without portal thrombosis.

Aged↗

[Extracorporeal lithotripsy in gallbladder lithiasis].

Extracorporeal shock-wave lithotripsy (ESWL) has been used since 1986 as an alternative to surgery for the treatment of uncomplicated gallstone disease, as it induces fragmentation of gallstones. The major determinant of fragmentation is the total stone volume. Lithotripsy must be associated with oral bile acid therapy to obtain a complete disappearance of the fragments. The methodological aspects, the criteria for inclusion and exclusion and the results of ESWL are discussed. The preliminary results seem to be satisfactory with regard to stone fragmentation and to safety. However, in order to determine exactly the place of ESWL in the treatment of gallstones, some questions must be answered: which are the best lithotripters, what are the best indications of ESWL, what is the rate of stone recurrence after successful therapy, what kind of monitoring is needed after the stones have disappeared? While this new therapeutic approach is being evaluated, ESWL must be applied only to symptomatic gallstones.

Bile Acids and Salts↗

Influence of fibrinolysis and percutaneous transluminal coronary angioplasty on the frequency of ventricular premature complexes.

This study evaluated the aggressive management of acute myocardial infarction to determine how it modifies the incidence of ventricular arrhythmias and of other determinants of prognosis during recovery. The population consisted of 344 consecutive survivors of acute myocardial infarction admitted to the hospital with chest pain and ST-segment elevation on the electrocardiogram. Three groups constituted the study population: 168 control patients treated conservatively or in whom fibrinolysis was unsuccessful, 73 patients successfully reperfused with intravenous streptokinase and 103 patients with both successful fibrinolysis and successful percutaneous transluminal coronary angioplasty (PTCA) of the artery responsible for the infarct. Early spontaneous angina occurred in 47 control patients (28%), 25 streptokinase patients, (34%) and, in significantly fewer number, 20 PTCA patients (19%, p less than 0.05). Similarly, exercise-induced ST-segment depression on the predischarge exercise treadmill test was less frequent with PTCA (p less than 0.05). The number of ventricular premature complexes (VPCs) on a 24-hour Holter recording was 40 +/- 123/hr in the control group and significantly less in the streptokinase (21 +/- 64, p less than 0.05) and PTCA groups (17 +/- 61, p less than 0.05). Three or more VPCs/hr were observed in 50% of the control patients, compared with 29% of the streptokinase and 27% of the PTCA patients (p less than 0.005). Mean radionuclide ejection fraction was greater than 40% and similar in the 3 study groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗

Differential colocalization of neuropeptide Y- and methionine-enkephalin-Arg6-Gly7-Leu8-like immunoreactivity in catecholaminergic neurons in the rat brain stem.

The present study, using a combination of catecholamine (CA) histofluorescence and peptide immunocytochemistry in the same tissue sections, investigated the coexistence of neuropeptide Y (NPY) and methionine-enkephalin-Arg6-Gly7-Leu8 (MEAGL)-like immunoreactivity (LI) in catecholaminergic neurons of colchicine-treated rat brain stems. Of the total number of catecholaminergic neurons in the A1/C1, A2/C2, A3, A4, and A6 regions approximately 83, 28, 98, 76, and 36%, respectively, contained both NPY-LI and CA. Of the total number of catecholaminergic neurons in A1/C1, A2/C2, A3, and A5 regions, approximately 47, 4, 8, and 17%, respectively, contained both MEAGL-LI and CA. Moreover, about 24% of the catecholaminergic neurons in the A1/C1 region contained both NPY- and MEAGL-LI. Neither the noradrenergic neurons (A7) in the pons nor any of the dopaminergic neurons in the midbrain (A8, A9, A10) contained NPY- or MEAGL-LI. Neurons containing both NPY- and MEAGL-like immunoreactive peptides without CA were not found in the rat brain stem. These findings indicate that catecholaminergic neurons in the brain stem of the rat can be subdivided into distinct subgroups on the basis of the coexistence of specific peptides.

Animals↗

Localization of atrial natriuretic factor (ANF) binding sites in the central nervous system of the frog.

The distribution of atrial natriuretic factor (ANF) binding sites was investigated in the central nervous system of the frog Rana ridibunda using the technique of in vitro receptor autoradiography by means of [125I]-labeled ANF-28. The anatomic distribution of ANF recognition sites was determined on Kodak ARX films apposed onto tissue sections, and their distribution was examined in greater detail by analysis of autoradiograms generated by using emulsion-coated sections. The highest levels of ANF binding sites were found in the olfactory bulb, the dorsal pallium, the septum, the habenular nucleus, the dorsal infundibular nucleus, the interpeduncular nucleus, and in the tectum. Moderate levels of ANF binding sites were observed in the thalamus and throughout the mesencephalon, whereas low levels were detected in the lateral and medial pallium, the medial forebrain bundle, and the nucleus rotondus. In the pituitary gland, the neural and distal lobes were densely loaded with ANF binding sites, whereas no autoradiographic labeling was observed in the pars intermedia. In general, there was a good correlation between the location of ANF receptors and the distribution of ANF-containing neurons, as previously determined by immunocytochemistry. Together these results support the view that ANF may act as a neurotransmitter or a neuromodulator in various regions of the frog brain.

Animals↗

Changes in hippocampal LH-RH receptor density during maturation and aging in the rat.

In earlier studies, we have reported the presence of luteinizing hormone-releasing hormone (LH-RH) binding sites in different rat brain areas including the hippocampus, lateral septum, amygdaloid nucleus and subiculum. We have also demonstrated that sex steroids can modulate the concentrations of brain LH-RH receptors. The role of hormonal status during different stages of development in regulating hippocampal LH-RH receptor concentration was assessed using in vitro autoradiography performed on slide-mounted frozen sections. Labeling was measured quantitatively by optical densitometry. Female and male rats of different ages (from birth to 21 months of age) were used in these experiments. The results obtained were similar in both sexes. As early as 6 days of age, LH-RH binding sites could be detected. The concentration of receptors increased with time and reached a maximum at 35 and 45 days of age for male and female, respectively. Thereafter, the receptor concentrations decreased and were at their minimum in middle-age animals. In older rats (17 and 21 months of age), LH-RH binding sites increased in concentration. These results suggest that, at the time of puberty, hormonal status induces an increase in the density of brain LH-RH receptors whilst in older rats, as previously demonstrated in castrated animals, the decreased production of gonadal hormones results in an increase in receptor concentration.

Aging↗

Beta-adrenergic receptors in DMBA-induced rat mammary tumors: correlation with progesterone receptor and tumor growth.

In order to gain further knowledge about the potential role of catecholamines in mammary carcinoma, we have used the potent beta-adrenergic antagonist cyanopindolol (CYP) as iodinated ligand to characterize beta-adrenergic receptors in membranes prepared from mammary tumors induced by dimethylbenz(a)anthracene (DMBA) administration in the rat. The binding of [125I]CYP to membrane preparations of DMBA-induced rat mammary tumors is rapid at room temperature, reaching half maximal specific binding at 30 min of incubation. Scatchard analysis of the data indicates that [125I]CYP binds to a single class of high affinity sites (114 +/- 2.1 fmoles/mg protein) at an apparent KD value of 38.0 +/- 0.3 pM. The order of potency of a series of agonists to compete for [125I]CYP binding is consistent with interaction with a beta 2-subtype receptor: zinterol greater than (-)isoproterenol greater than (-)epinephrine much greater than (-)norepinephrine. In addition, the potency of a series of specific beta 1 and beta 2 synthetic compounds to displace [125I]CYP in mammary tumors is similar to their potency in typical beta 2-adrenergic tissues. The binding of [125I]CYP to DMBA-induced rat mammary tumors shows a marked stereoselectivity, the (-)isomers of isoproterenol and propranolol being 150 and 80 times more potent, respectively, than their respective enantiomers. The autoradiographic localization of [125I]CYP performed on frozen sections revealed the presence of specific beta-adrenergic receptors in all the malignant cells. Spontaneous mammary tumors of aging (18-22 months) female rats have high levels of beta-adrenergic receptors. Castration decreased the concentration of [125I]CYP binding sites in DMBA-induced mammary tumors. A close correlation was observed between progressing, static, and regressing tumors after ovariectomy and beta-adrenergic receptor concentration. The presence of beta-adrenergic receptors in mammary tumors as well as the modulation of their level by ovarian hormones provides a mechanism for catecholaminergic influence in mammary cancer tissue.

9,10-Dimethyl-1,2-benzanthracene↗