Pulsatile Hormone Release

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William B Wehrenberg - One of the best experts on this subject based on the ideXlab platform.

  • effects of repeated doses and continuous infusions of the growth Hormone releasing peptide hexarelin in conscious male rats
    Journal of Endocrinology, 1998
    Co-Authors: Lisa K. Conley, Rebecca S. Brogan, Andrea Giustina, Rolf C Gaillard, William B Wehrenberg
    Abstract:

    We have previously shown that hexarelin, a novel GHreleasing peptide (GHRP), is able to elicit GH Release when administered i.v., s.c. or by mouth and that it is a more potent GH secretagogue than GHRP-6. In the current study, we investigated the eVects of hexarelin administered as repeated doses at 2 h intervals or as a continuous 6, 30 or 174 h infusion to conscious male rats. In the first experiment, adult male Sprague‐Dawley rats were prepared with dual indwelling jugular catheters. On the day of experimentation, these animals received three 25 µg/kg i.v. boluses of hexarelin at 2 h intervals with blood sampling at 5, 10, 15, 30, 60, 90 and 120 min after each dose. The mean peak GH response and the mean area under the GH response curve (AUC) for the 30 min after each administration were calculated and are reported as the means AUC 5585&700 ng/ml per 30 min) and second (peak 149&47 ng/ml; AUC 3056&908 ng/ml per 30 min) injections of hexarelin, but not between the first and third (peak 214&49 ng/ml; AUC 3862&844 ng/ml per 30 min). In a second series of experiments, adult male Sprague‐Dawley rats received continuous infusions (100 µg/h) of hexarelin or saline (1 ml/h) for 6, 30 or 174 h. Blood samples were collected every 20 min for the duration of the 6 h infusion and for the last 6 h of the two longer hexarelin infusions. Plasma GH concentrations peaked within 40 min of the initiation of infusion, but soon returned to basal levels. Mean plasma GH concentrations did not diVer between any of the treatment groups, nor did any of the parameters of Pulsatile Hormone Release analyzed. No significant diVerences in plasma corticosterone concentrations were noted between any of the treatment groups. On the other hand, while neither the 6 h (941&70 ng/ml) nor the 30 h (954&70 ng/ml) hexarelin infusions resulted in a significant increase in the plasma IGF-I concentrations over those noted in the saline controls (935&65 ng/ml), a 174 h hexarelin infusion did elicit a significant increase (1289&42 ng/ml; P<0·05). Thus it appears that, while continuous exposure to hexarelin does not disrupt normal GH cycling, it may (after up to 174 h of exposure) alter other components of the growth axis. In addition, since the character of Pulsatile GH Release remained unaltered in response to the hexarelin infusion, it appears that this GHRP may not act by suppression of functional somatostatin tone as has been suggested previously.

Johannes D Veldhuis - One of the best experts on this subject based on the ideXlab platform.

  • nature of altered Pulsatile Hormone Release and neuroendocrine network signalling in human ageing clinical studies of the somatotropic gonadotropic corticotropic and insulin axes
    Novartis Foundation symposium, 2000
    Co-Authors: Johannes D Veldhuis
    Abstract:

    Recent clinical investigations have implemented an array of new analytical tools to evaluate the neuroregulation of endocrine axes. These studies demonstrate multifold disruption within the growth Hormone (GH), luteinizing Hormone (LH)-testosterone, adrenocorticotropin (ACTH)-cortisol and the insulin axes in healthy ageing men and women. Novel research strategies in ageing include such developments as the indirect in vivo assessment of neuroendocrine network integration, via the approximate entropy (ApEn) statistic to monitor the unihormonal orderliness and bihormonal synchronicity of Hormone Release, and thus infer stability of network-integrative processes. For example, ApEn calculations show that the individual orderliness of GH, insulin or LH Release falls progressively in older men and women, and the conditional synchrony between LH and testosterone (or LH and follicle-stimulating Hormone/prolactin) Release, and LH secretion and the neurogenically organized signal, nocturnal penile tumescence (NPT), all decline markedly in older men. Evaluation of the ACTH-cortisol axis points additionally to disrupted bihormonal synchrony within this stress-responsive system in healthy ageing. A complementary investigative tool, viz. a stochastic differential equation random-effects feedback construct of the interactive male gonadotropin-releasing Hormone-LH-testosterone axis, predicts that only certain extant postulates of ageing in the male reproductive axis will give rise to the observed erosion of LH-testosterone synchrony. Collectively, available clinical data suggest a general model of early neuroendocrine ageing in the human, in both the male and female, wherein ageing is marked by variable disruption in the time-delayed feedback and feedforward interconnections among neuroendocrine glands, which constitute an integrated axis and which control the joint synchrony of Hormone Release.

Lisa K. Conley - One of the best experts on this subject based on the ideXlab platform.

  • effects of repeated doses and continuous infusions of the growth Hormone releasing peptide hexarelin in conscious male rats
    Journal of Endocrinology, 1998
    Co-Authors: Lisa K. Conley, Rebecca S. Brogan, Andrea Giustina, Rolf C Gaillard, William B Wehrenberg
    Abstract:

    We have previously shown that hexarelin, a novel GHreleasing peptide (GHRP), is able to elicit GH Release when administered i.v., s.c. or by mouth and that it is a more potent GH secretagogue than GHRP-6. In the current study, we investigated the eVects of hexarelin administered as repeated doses at 2 h intervals or as a continuous 6, 30 or 174 h infusion to conscious male rats. In the first experiment, adult male Sprague‐Dawley rats were prepared with dual indwelling jugular catheters. On the day of experimentation, these animals received three 25 µg/kg i.v. boluses of hexarelin at 2 h intervals with blood sampling at 5, 10, 15, 30, 60, 90 and 120 min after each dose. The mean peak GH response and the mean area under the GH response curve (AUC) for the 30 min after each administration were calculated and are reported as the means AUC 5585&700 ng/ml per 30 min) and second (peak 149&47 ng/ml; AUC 3056&908 ng/ml per 30 min) injections of hexarelin, but not between the first and third (peak 214&49 ng/ml; AUC 3862&844 ng/ml per 30 min). In a second series of experiments, adult male Sprague‐Dawley rats received continuous infusions (100 µg/h) of hexarelin or saline (1 ml/h) for 6, 30 or 174 h. Blood samples were collected every 20 min for the duration of the 6 h infusion and for the last 6 h of the two longer hexarelin infusions. Plasma GH concentrations peaked within 40 min of the initiation of infusion, but soon returned to basal levels. Mean plasma GH concentrations did not diVer between any of the treatment groups, nor did any of the parameters of Pulsatile Hormone Release analyzed. No significant diVerences in plasma corticosterone concentrations were noted between any of the treatment groups. On the other hand, while neither the 6 h (941&70 ng/ml) nor the 30 h (954&70 ng/ml) hexarelin infusions resulted in a significant increase in the plasma IGF-I concentrations over those noted in the saline controls (935&65 ng/ml), a 174 h hexarelin infusion did elicit a significant increase (1289&42 ng/ml; P<0·05). Thus it appears that, while continuous exposure to hexarelin does not disrupt normal GH cycling, it may (after up to 174 h of exposure) alter other components of the growth axis. In addition, since the character of Pulsatile GH Release remained unaltered in response to the hexarelin infusion, it appears that this GHRP may not act by suppression of functional somatostatin tone as has been suggested previously.

Rebecca S. Brogan - One of the best experts on this subject based on the ideXlab platform.

  • effects of repeated doses and continuous infusions of the growth Hormone releasing peptide hexarelin in conscious male rats
    Journal of Endocrinology, 1998
    Co-Authors: Lisa K. Conley, Rebecca S. Brogan, Andrea Giustina, Rolf C Gaillard, William B Wehrenberg
    Abstract:

    We have previously shown that hexarelin, a novel GHreleasing peptide (GHRP), is able to elicit GH Release when administered i.v., s.c. or by mouth and that it is a more potent GH secretagogue than GHRP-6. In the current study, we investigated the eVects of hexarelin administered as repeated doses at 2 h intervals or as a continuous 6, 30 or 174 h infusion to conscious male rats. In the first experiment, adult male Sprague‐Dawley rats were prepared with dual indwelling jugular catheters. On the day of experimentation, these animals received three 25 µg/kg i.v. boluses of hexarelin at 2 h intervals with blood sampling at 5, 10, 15, 30, 60, 90 and 120 min after each dose. The mean peak GH response and the mean area under the GH response curve (AUC) for the 30 min after each administration were calculated and are reported as the means AUC 5585&700 ng/ml per 30 min) and second (peak 149&47 ng/ml; AUC 3056&908 ng/ml per 30 min) injections of hexarelin, but not between the first and third (peak 214&49 ng/ml; AUC 3862&844 ng/ml per 30 min). In a second series of experiments, adult male Sprague‐Dawley rats received continuous infusions (100 µg/h) of hexarelin or saline (1 ml/h) for 6, 30 or 174 h. Blood samples were collected every 20 min for the duration of the 6 h infusion and for the last 6 h of the two longer hexarelin infusions. Plasma GH concentrations peaked within 40 min of the initiation of infusion, but soon returned to basal levels. Mean plasma GH concentrations did not diVer between any of the treatment groups, nor did any of the parameters of Pulsatile Hormone Release analyzed. No significant diVerences in plasma corticosterone concentrations were noted between any of the treatment groups. On the other hand, while neither the 6 h (941&70 ng/ml) nor the 30 h (954&70 ng/ml) hexarelin infusions resulted in a significant increase in the plasma IGF-I concentrations over those noted in the saline controls (935&65 ng/ml), a 174 h hexarelin infusion did elicit a significant increase (1289&42 ng/ml; P<0·05). Thus it appears that, while continuous exposure to hexarelin does not disrupt normal GH cycling, it may (after up to 174 h of exposure) alter other components of the growth axis. In addition, since the character of Pulsatile GH Release remained unaltered in response to the hexarelin infusion, it appears that this GHRP may not act by suppression of functional somatostatin tone as has been suggested previously.

Andrea Giustina - One of the best experts on this subject based on the ideXlab platform.

  • effects of repeated doses and continuous infusions of the growth Hormone releasing peptide hexarelin in conscious male rats
    Journal of Endocrinology, 1998
    Co-Authors: Lisa K. Conley, Rebecca S. Brogan, Andrea Giustina, Rolf C Gaillard, William B Wehrenberg
    Abstract:

    We have previously shown that hexarelin, a novel GHreleasing peptide (GHRP), is able to elicit GH Release when administered i.v., s.c. or by mouth and that it is a more potent GH secretagogue than GHRP-6. In the current study, we investigated the eVects of hexarelin administered as repeated doses at 2 h intervals or as a continuous 6, 30 or 174 h infusion to conscious male rats. In the first experiment, adult male Sprague‐Dawley rats were prepared with dual indwelling jugular catheters. On the day of experimentation, these animals received three 25 µg/kg i.v. boluses of hexarelin at 2 h intervals with blood sampling at 5, 10, 15, 30, 60, 90 and 120 min after each dose. The mean peak GH response and the mean area under the GH response curve (AUC) for the 30 min after each administration were calculated and are reported as the means AUC 5585&700 ng/ml per 30 min) and second (peak 149&47 ng/ml; AUC 3056&908 ng/ml per 30 min) injections of hexarelin, but not between the first and third (peak 214&49 ng/ml; AUC 3862&844 ng/ml per 30 min). In a second series of experiments, adult male Sprague‐Dawley rats received continuous infusions (100 µg/h) of hexarelin or saline (1 ml/h) for 6, 30 or 174 h. Blood samples were collected every 20 min for the duration of the 6 h infusion and for the last 6 h of the two longer hexarelin infusions. Plasma GH concentrations peaked within 40 min of the initiation of infusion, but soon returned to basal levels. Mean plasma GH concentrations did not diVer between any of the treatment groups, nor did any of the parameters of Pulsatile Hormone Release analyzed. No significant diVerences in plasma corticosterone concentrations were noted between any of the treatment groups. On the other hand, while neither the 6 h (941&70 ng/ml) nor the 30 h (954&70 ng/ml) hexarelin infusions resulted in a significant increase in the plasma IGF-I concentrations over those noted in the saline controls (935&65 ng/ml), a 174 h hexarelin infusion did elicit a significant increase (1289&42 ng/ml; P<0·05). Thus it appears that, while continuous exposure to hexarelin does not disrupt normal GH cycling, it may (after up to 174 h of exposure) alter other components of the growth axis. In addition, since the character of Pulsatile GH Release remained unaltered in response to the hexarelin infusion, it appears that this GHRP may not act by suppression of functional somatostatin tone as has been suggested previously.