Regulation Of The Ensemble Hypothalamopituitaryleydig Cell Axis

An emergent thesis in neuroendocrine research is that early disruption of (negative) feedback and/or (positive) feedforward may be detectable without any demon-

Secretion Pulsatile Testost Rone
Fig. 5. (Continued) (B) Deconvolution estimates of basal (top), pulsatile (middle), and total (bottom) daily LH secretion in young and older men. Numerical values are the mean ± SEM (median). P values are estimated by the rank-sum test. p = NS denotes < 0.05. (Adapted from ref. 38.)

strable change in overall hormone production (28,30,35,39,40). The foregoing insight is relevant to understanding early disarray of the hypothalamic-pituitary-gonadal axis in aging. Therein, we adopt the basic precept that repeated, dose-dependent, time-delayed adjustments in regulatory sites govern systemic androgen availability in a homeostatic fashion (38,66,82-89). To aid intuition, we have formalized core feedback connections among GnRH, LH and testosterone mathematically (38,81-83) A simplified model structure predicts that jointly impaired feedforward by LH and feedback by testosterone would yield a high-frequency, low-amplitude, and disorderly pattern of LH release. On the other hand, isolated failure of GnRH outflow would explain only inappropriately low LH concentrations and attendant hypoandrogenemia but not an elevated LH pulse frequency or irregular release patterns (39,40). Exploration of this ensemble concept requires more focused assessment of physiological regulation, as highlighted next.

Regulation Testosterone Levels

Fig. 6. Diminution in luteinizing hormone (LH) secretory-burst mass and acceleration of LH pulse frequency in aging when compared with young men inferred by two deconvolution methods (40). (A) LH concentration profiles (± sample SDs) measured in serum collected every 10 min for 24 h and analyzed by immunoradiometric assays and variable-waveform (stochastic differential equation-based) deconvolution analysis (predicted continuous curve) (38).(Figure continues)

Fig. 6. Diminution in luteinizing hormone (LH) secretory-burst mass and acceleration of LH pulse frequency in aging when compared with young men inferred by two deconvolution methods (40). (A) LH concentration profiles (± sample SDs) measured in serum collected every 10 min for 24 h and analyzed by immunoradiometric assays and variable-waveform (stochastic differential equation-based) deconvolution analysis (predicted continuous curve) (38).(Figure continues)

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