Ultradian oscillations in somatostatin and growth hormone-releasing hormone mRNAs in the brains of adult male rats.

Abstract

In the adult male rat, growth hormone (GH) secretion is characterized by an ultradian rhythin generated by the rhythmic interplay of the stimulatory effects of GHreleasing hormone (GHRH) and the inhibitory effects of somatostatin (Ss). Although considerable evidence indicates that GHRH and Ss are secreted in reciprocal 3-to 4-hr rhythms, the mechanism underlying the rhythmic secretion of these two neuropeptides is unknown. We tested the hypothesis that the rhythmic and reciprocal oscillations in secretion of Ss and GHRH are associated with parallel changes in synthesis and that this would be reflected by coincident oscillations in levels of the respective mRNAs. In the first experiment, Ss mRNA was significantly greater in the periventricular nucleus of animals sacrificed at the time of a presumed peak in the GH rhythm than in animals sacrificed at the time of a presumed trough; this variation was limited to the anterior third of this nucleus. Conversely, GHRH mRNA content throughout the arcuate nucleus was significantly greater at the time of a GH trough. In the second experiment, groups of animals were sacrificed during two consecutive cycles. In this set of animals, Ss mRNA content was 40% greater (P < 0.005) during peak GH concentrations, whereas GBRH mRNA content was 42% greater (P < 0.005) during the GH trough. This difference persisted when the two cycles were analyzed separately. The findings that the cellular nIRNA content for Ss and GHRH varies in a reciprocal manner with the presumed secretion of these neuropeptides suggest that, like secretion, the synthesis of Ss and GHRH also varies rhythmically. The occurrence of this rhythm suggests a model for a transcriptional oscillator that may subserve the generation of this and possibly other neuroendocrine rhythms.In the adult male rat, the secretion of growth hormone (GH) is characterized by an endogenous ultradian rhythm. Highamplitude secretory bursts occur at regular 3.3-hr intervals and are separated by intervening troughs during which basal GH levels are undetectable (1). The patterning of GH secretion is generated by the interplay of the stimulatory effects of GH-releasing hormone (GHRH) and the inhibitory effects of somatostatin (Ss) (for review, see ref.2). In the rat, these two neuropeptides are released in reciprocal 3-to 4-hr cycles and act upon the pituitary somatotropes to generate the ultradian rhythm of GH secretion (3, 4). The primary source of median eminence Ss is from neurons in the periventricular nucleus (PeN) (5), whereas the primary source of GHRH is from neurons in the arcuate nucleus (Arc) (6).Although it is known that the rhythmic oscillation of GH secretion is governed by Ss and GHRH, the mechanisms underlying the rhythmic discharge of Ss and GHRH neurons remain to be elucidated. On the one hand, these discharge patterns could reflect the intrinsic properties of the peptidergic neurons themselves. Alternatively, it is conceivable that the oscillations reflect interactions among the elements of a feedback loop involving G...

Effect of nutrient restriction on the somatotropes and substance P-immunoreactive cells in the pituitary of the female ovine fetus

“…The fetal somatostatin system does not mature until after parturition [14,[53][54][55][56][57]. Increased fetal GH secretion [18,[22][23][24] may be due to somatotrope sensitivity to GHRH and the immaturity of the somatostatin system [14,54,58,59].…”

Hypophysiotropic Somatostatin Expression during Postnatal Development in Growth Hormone-Deficient Ames Dwarf Mice: mRNA in situ Hybridization

“…The pulsatile pattern of growth hormone (GH) secre tion is controlled by coordinated hypothalamic produc tion of two peptides, stimulatory GH-releasing hormone (GHRH) and inhibitory somatostatin (somatotropin re lease-inhibiting hormone, SRIH) [1], SRIH is expressed in many brain regions [2], but only neurons in the anterior periventricular nucleus (PeN) project to the median emi nence to deliver SRIH to the hypophysial portal vascula ture [3]. SRIH production in these hypothalamic neurons is pulsatile, both for peptide secretion [4] and mRNA lev els [5], producing phases of high SRIH, inhibiting GH secretion, alternating with periods of lowered SRIH, and GH release [1,4,6]. …”

No effect of nutrient restriction from gestational days 28 to 78 on immunocytochemically detectable growth hormone-releasing hormone (GHRH) neurons and GHRH receptor colocalization in somatotropes of the ovine female fetus

“…Evidence suggests that the fetal somatostatin system does not mature until after parturition in altricial species (Gluckman et al, 1979;Bassett and Gluckman, 1986;de Zegher et al, 1989;Zeitler et al, 1991;Polkowska, 1995;Muller et al, 1999). Increased fetal GH secretion under normal conditions (Bassett and Madill, 1974;Koritnik et al, 1981;Schaefer et al, 1984;Bauer et al, 1995) has been attributed to somatotrope sensitivity to GHRH and the immaturity of the somatostatin system (Blanchard et al, 1988;de Zegher et al, 1989;Goodyer et al, 1993;Muller et al, 1999).…”

“…In the fetus of atricial species, evidence suggests that the somatostatin system does not mature until after parturition (Gluckman et al, 1979;Bassett and Gluckman, 1986;de Zegher et al, 1989;Zeitler et al, 1991;Polkowska, 1995;Muller et al, 1999). However, perturbed GHRH secretion could provide the mechanism for the altered GH secretory patterns seen during gestational nutrient restriction (Bauer et al, 1995;Boguszewski et al, 1997).…”