Hypophyseal-portal somatostatin (SRIF) and jugular venous growth hormone secretion in the conscious unrestrained ewe

Abstract

Somatostatin (SRIH) release into hypophyseal portal blood varies reciprocally with growth hormone (GH) pulse generation in the male rat. However, few studies have directly evaluated this relationship in the female of any species. To address this issue, we carried out intensive (5 min) and extended (240 min) simultaneous monitoring of hypophyseal portal SRIH and internal jugular GH secretion in 7 unanesthetized ewes. Bihormonal synchrony was assessed by three statistically independent but complementary analyses: (i) cross-approximate entropy (X-ApEn) analysis to appraise the conditional regularity of SRIH/GH release patterns; (ii) cross-correlation analysis of paired sample SRIH and GH release rates, and (iii) probability analysis of random versus nonrandom SRIH and GH discrete pulse concordance. From a one-variable perspective, ApEn analysis documented consistently more irregular patterns of SRIH than GH release (94 +/- 4.3 and 72 +/- 8.1%, respectively, of the mean irregularity of 1,000 individual random-shuffled cognate series, p = 0.034). From a two-variable perspective, X-ApEn analysis revealed a nearly mean random relationship between SRIH and GH release patterns (group mean +/- SEM, 94 +/- 4.5% of the mean asynchrony of 1,000 randomly shuffled SRIH/GH pairs). Cross-correlation analysis disclosed highly variable linkages between SRIH and GH secretion; viz, negative cross-correlations in 5 sheep, positive relationships in 4, and both positive and negative SRIH/GH associations in 2 animals, wherein changes in SRIH secretion either preceded or followed those of GH. Peak detection by model-free cluster analysis quantified a total of 28 SRIH and 31 GH release episodes. Corresponding interpulse intervals (min) were comparable (37 +/- 4 (SRIH) and 43 +/- 12 (GH)), but the mean fractional (%) amplitude of SRIH peaks was 3.5-fold lower (60 +/- 10%) than that for GH (225 +/- 50%) (p = 0.024). Pulse-concordance probability testing showed that discrete peaks of SRIH and GH secretion coincided only 33% of the time, although this value exceeded chance expectation (p < 10(-4)). In summary, the present analysis applies intensive (5 min) and extended (240 min) simultaneous sampling of hypophyseal-portal and jugular venous blood to quantitate the degree of coordinate SRIH and GH secretion in the unanesthetized ovariectomized ewe. Thereby, we unmask highly irregular SRIH release patterns, and nearly random SRIH and GH associations. We conclude that, to the extent that in vivo sampling reflects physiological SRIH/somatotrope activity, the female sheep maintains complex time-varying interactions between SRIH and GH release.