In vivo Alterations in the Gonadotropin-Releasing Hormone Pulse Generator and the Secretion and Clearance of Luteinizing Hormone in the Uremic Castrate Rat
Notice bibliographique
Résumé
To investigate the mechanisms subserving the reported alterations in the pulsatile release of LH in uremia, we simultaneously studied endogenous accumulation of GnRH in the pituitary gland and the secretion and clearance of LH in vivo in experimentally uremic, orchidectomized rats. The temporal pattern of GnRH secretion was assessed by intrapituitary microdialysis, the dynamics of plasma LH by continuous exchange transfusion. Studies were performed in rats rendered uremic by subtotal nephrectomy (n = 8) and control rats which were either fed ad libitum (n = 8) or pair-fed with the uremic animals (n = 8). Blood samples were obtained at 5-min and microdialysate samples at 10-min intervals over a period of 270 min. The pulsatile secretory characteristics of GnRH and LH and the half-life of plasma LH were estimated by multiple-parameter deconvolution analysis. The temporal relationship between the hormone concentrations and between the secretory events of GnRH and LH was assessed by cross-correlation analysis and hypergeometric coincidence analysis. We observed that: (1) the estimated half-life of plasma LH was prolonged in uremic (59 ± 10 min) rats compared to ad libitum-fed (17 ± 3 min, p = 0.014) and pair-fed controls (19 ± 3 min, p = 0.025); (2) the LH production rate was decreased in uremic animals (18 ± 5 ng/ml·270 min) compared to ad libitum-fed (37 ± 4 ng/ml-270 min, p = 0.002) and pair-fed controls (48 ± 9 ng/ml·270 min, p = 0.0006); (3) the reduction of LH secretion rate in the uremic animals was accounted for by a decrease in detectable LH pulse frequency (2.1 ± 0.2 peaks/h) compared to ad libitum-fed (3.1 ± 0.1 peaks/h, p = 0.01) and pair-fed controls (2.8 ± 0.2 peaks/h, p = 0.06) and a diminished mass of hormone released per burst (uremic 1.8 ± 0.2 ng/ml, ad libitum-fed 2.6 ± 0.3 ng/ml, p = 0.05, pair-fed 3.8 ± 0.8 ng/ml, p = 0.025); (4) the secretion rate of GnRH was reduced to a similar degree in uremic rats (180 ± 15 pg/tube -270 min, p = 0.04) and pair-fed controls (170 ± 26 pg/tube-270 min, p = 0.04) compared to ad libitum-fed controls (270 ± 36 pg/ tube-270 min). In contrast to the reduced number of detectable LH secretory events, the frequency of GnRH secretory peaks in uremic rats was not different from ad libitum-fed and pair-fed controls. The reduced GnRH secretion rate in uremic and pairfed animals was entirely attributable to a decrease mass of GnRH released per burst (uremic 18+ 1.5, p = 0.06; pair-fed 17 ± 2.2, p = 0.046; ad libitum-fed 27 + 3.6 pg/tube); (5) the number of coincident GnRH and LH secretory events exceeded the rate expected by chance alone (p < 10-5) in all three groups of animals. Cross-correlation analysis showed the highest concordance between GnRH and LH for LH concentrations lagging GnRH by 0-5 min. Eighty-two percent of the GnRH impulses observed in the control groups, but only 62% in the uremic group coincided within + 5 min with a GnRH impulse. In conclusion, our findings indicate that reduced metabolic clearance masks pituitary hyposecretion of LH in uremic rats. Decreased LH production results from a reduction in GnRH impulse strength and altered hypothalamo-pituitary signal transduction. The former finding may be related to mild malnutrition and/or paracrine autoregulation, while the latter appears to be uremia-specific.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».