Te SHBGTe SHBG

Time

Diffusion Advection k3||k4 2

► Binding Metabolism

Fig. 10. (Continued) (B) Schema of fate of secreted testosterone in plasma. (Unpublished line drawing.)

Developing concepts of time-adaptive control of testosterone secretion incorporate interactions among GnRH, LH, and testosterone. Homeostasis requires reversible, recurrent, and reciprocal (feedback and feedforward) adjustments to external stress (e.g., food deprivation and trauma) and internal needs (e.g., anabolism and procreation). In this ensemble perspective, no single gland acts alone. Clinical studies in the healthy aging male point to regulatory failure of GnRH-driven pulsatile LH secretion, LH-stimulated Leydig cell androgen biosynthesis, and testosterone-enforced feedback on GnRH/LH outflow. Accordingly, hypoandrogenemia in the older male is the final common consequence of a matrix of primary and secondary deficits in the hypothala-mic-pituitary-gonadal ensemble.

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