We have applied explicit probability equations to assess possible non-random associations among four distinct hormone series consisting of episodic luteinizing hormone, follicle stimulating hormone, β-endorphin, and/or cortisol pulses observed under physiological conditions in normal men. Closed-form likelihood functions permitted us to demonstrate significantly coordinated patterns of multiple hormone release. A specific quadruple co-pulsatility pattern was observed, in which the two gonadotropic hormones (luteinizing hormone and follicle stimulating hormone) were co-secreted and coupled by a 10-20 min lag to the later release of β-endorphin. In turn, β-endorphin release episodes were followed within 0-30 min by cortisol bursts. Conditional probability analysis allowed us to reject with high statistical confidence the null hypothesis that this unique temporally specified pattern of quadruple hormone release was due to purely random associations among the four pulsatile series. We conclude that discrete hormone release episodes associated with four hormones within the gonadotropic and corticotropic axes in man exhibit significantly lagged non-random temporal coupling in vivo.
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