Hypophyseal-Portal Somatostatin (SRIH) 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.

Effects of Estrogen on Growth Hormone Pulsatility in Peripheral Blood and Neuropeptide Profiles in the Cerebrospinal Fluid of Goats

“…To analyze fluctuations in the pulse/trough profiles during these periods, Tukey-Kramer's posthoc test was used for multiple comparisons. Coincidence between a GH pulse and neuropeptide pulse/trough was evaluated as described previously [17,22,34]. Random data for GH pulse and neuropeptide pulse/trough series obtained with Monte Carlo shuffling (n=1,000) were used as a control.…”

Joint pituitary-hypothalamic and intrahypothalamic autofeedback construct of pulsatile growth hormone secretion

“…Experimental data show that GH-dependent feedback on SRIF neurons is attenuated, but not abolished, in the adult female rat (15,19,20,31,34,37,38,42). In the current formulation, partial, rather than complete, muting of GH autoinhibition in the female animal predicts occasional epochs of pluriphasic GH release, as observed under intensive (5-min) and extended (6-to 24-h) monitoring of GH secretion in the female rodent and ruminant (19,38,42,49). A comparable inference of disinhibited GHRH-SRIF oscillatory activity would apply to the nearly continuous train of GH secretory bursts in the presumptively low SRIF milieu associated with fasting or deep sleep in the human (22,26).…”

“…However, we report greater irregularity of SRIF than GH release using 5-min sampling of cavernous-sinus blood in the conscious unrestrained ewe (SRIF and GH ApEn values were 94 Ϯ 4.3 and 72 Ϯ 8.1%, respectively, of the mean irregularity of 1,000 individual random-shuffled cognate series; P ϭ 0.034; Ref. 49).…”

“…This two-oscillator formulation explicates (but does not prove) 1) the GHRH-sensitizing action of prior SRIF exposure; 2) a three-site (intrahypothalamic, hypothalamo-pituitary, and somatotrope GH store dependent) mechanism driving rebound-like GH secretion after SRIF withdrawal in the male; 3) an obligatory role for pituitary GH stores in representing rebound GH release in the female; 4) greater irregularity of SRIF than GH release profiles; and 5) a basis for the paradoxical GH-inhibiting action of centrally delivered GHRH. feedback; mathematical model; somatotropic axis; hormone pulsatility; somatostatin; growth hormone-releasing hormone; hypothalamus THE SECRETION OF GROWTH HORMONE (GH) is pulsatile in the human, monkey, sheep, swine, guinea pig, rat, and mouse (10,20,21,30,34,37,40,48,49). In the rodent, episodic GH release directs somatic growth, cellular gene expression, and autonegative feedback (3,20,31,34,37,42).…”

“…A distinctive feature of pulsatile GH secretion is the dual representation of 1) multiburst volleys, which recur every 3-3.5 h in the adult male rat and every 1.5-2.5 h in men and women, and 2) rapid discrete GH pulses, which arise every 30-60 min within an individual volley (19-22, 30, 37, 38, 42, 48, 49). Such complex patterns of GH release are evident by high-frequency (0.5-and 5-min) sampling paradigms in the unanesthetized rat, sheep, and healthy human (19,22,23,37,38,42,49). The mechanisms that generate composite low-frequency volleys and high-frequency GH bursts are not established.…”