NONCLASSICAL SECRETORY DYNAMICS OF LH REVEALED BY HYPOTHALAMOHYPOPHYSEAL PORTAL SAMPLING OF SHEEP

Continuous withdrawal of hypophyseal portal blood from unrestrained sh eep has permitted detailed assessments of the pulsatile secretion of g onadotrophin-releasing hormone (GnRH). To determine if this blood can also be used to characterize the secretory dynamics of pituitary hormo nes, patterns of luteinizing hormone (LH) in the hypophyseal portal bl ood of ovariectomized ewes was compared with previous patterns of GnRH and peripheral LH. Hypophyseal portal blood and jugular vein blood we re collected every 5 min from six ovariectomized ewes over 6-12 h. Hyp ophyseal portal blood contained GnRH-associated, sharply defined LH pu lses that were much larger than in the periphery. Pulses of secreted L H (hypophyseal portal LH less peripheral LH) showed much faster rates of rise and fall than peripheral and followed pulses of GnRH by an ave rage of 1.26 min. In contrast to pulses in jugular blood, secreted LH pulses often reached a relatively unchanging interpulse nadir-plateau and thereby approached closely algorithm-estimated, extrapolated basel ines. The interpulse baseline concentrations of secreted LH (99.6 ng/m L) in hypophyseal portal blood were 31-fold higher than those for jugu lar LH (3.23 ng/mL). These elevated concentrations also exceeded mean jugular peak concentrations (11.1 ng/mL) and, thus, primarily must rep resent newly secreted LH. The non-Gaussian profiles of th is secreted LH were substantially more complex than the inputs predicted from jugu lar LH measurements by deconvolution. Furthermore, regardless of the a nalytical approach, estimations of the mass of secreted LH in each pul se did not correlate well with inputs predicted by deconvolution or Ku shler-Brown pulsefit analysis of corresponding pulses in jugular blood (r(2) ranging 0.40-0.48). Among alternative explanations is the possi bility of heterogeneity in concentrations of GnRH in the portal vessel s and variable distribution within the hypophysis. in summary, assay o f hypophyseal portal blood obtained directly from the pituitary provid es a method for direct assessment of secretory responses to hypothalam ic peptides, and thereby serves as an unmatched method for studying th e dynamics of LH secretion in vivo. With this approach, LH is revealed to be secreted as complex, non-Gaussian pulses that are far more shar ply defined than those in the periphery, include non-GnRH-dependent, s ecretory components that cannot be predicted by deconvolution and are followed by periods of relatively constant, basal secretion.