The Anterior Periventricular Hypothalamus Is the Site of Somatostatin Inhibition on Its Own Release: An in vitro and Immunocytochemical Study

Abstract

The site of action of the inhibitory effect of somatostatin (SRIF) on its own release was studied by: (1) measuring SRIF release in vitro from tissue preparations containing either the proximal (periventricular hypothalamus) or the distal (median eminence) portions of the hypothalamic SRIF neurons, and (2) immunocytochemical investigation of the interconnections occurring between SRIF neuronal elements in these hypothalamic regions. In vitro, a biologically active, but noncross-reacting SRIF analog (D-Trp8 SRIF) in the RIA, inhibited 25 mM K⁺ induced SRIF release from anterior periventricular hypothalamic tissues. The inhibitory effect of D-Trp8 SRIF was dose-dependent, maximal at 10^–7M, and restricted to this anterior region, since median-eminence SRIF release was not modified by the presence of D-Trp8 SRIF. Additionally, LHRH release from anterior periventricular hypothalamus was unchanged in the presence of D-Trp8 SRIF. In the periventricular nucleus, perikarya and dendrites of labeled SRIF neurons showed frequent apposition of their limiting membranes. Classical synapses were also observed between SRIF-containing axonal processes and labeled perikarya or dendrites. Although membrane appositions between neighboring SRIF axons frequently occurred in the median eminence, no synaptic-like SRIF-SRIF connections could be detected at this level. The data demonstrate a direct inhibitory action of a SRIF agonist on the anterior periventricular hypothalamic release of the peptide. This effect correlates well with the occurrence of SRIF-SRIF synapses in this region; suggesting that SRIF exerts a negative feedback in the control of its own release through autoreceptors located on the perikarya or dendrites of SRIF-containing neurons.

Somatostatin Inhibits Alpha-2-Adrenergic-Induced Secretion of Growth Hormone-Releasing Hormone

“…However, our data clearly show that blockade of SRIH stimulates secretion of SRIH. This finding supports and extends those of others who showed that SRIH acts via an ultra short-loop negative feedback mechanism to inhibit expression of SRIH mRNA in the PeVN and release of SRIH from terminals in the median eminence [32, 33, 34]. The site of this inhibitory autoregulation is likely on axon terminals of SRIH neurons as shown in figure 7 because cyclo-SRIH increased release of SRIH from hypophysial stalk explants, which excludes the cell bodies of these neurons.…”

Interrelationships between Somatostatin sst2A Receptors and Somatostatin-Containing Axons in Rat Brain: Evidence for Regulation of Cell Surface Receptors by Endogenous Somatostatin

“…These observations suggest that SRI F may be in a position to regulate the activity of SRIF neurons, and presumably its own release, in several brain structures. Because our experiments were conducted in noncolchicinetreated rats (to optimize visualization of axon terminals), it is likely that colocalization of sst2A receptors and SRIF is more pervasive than our results and than earlier f unctional studies (Peterfreund and Vale, 1984;Epelbaum et al, 1986;Richardson and T wente, 1986) had led us to believe.…”

<b>Neurotrophins in Neuroendocrine Control: Brain Derived-neurotrophic Factor (BDNF) and Somatostatin Involvement in the Stress Response and Reproductive Physiology <b/>

“…In contrast, since stress induces a BDNF mRNA decrease in the PeV nucleus (Arancibia et al, 2000 b ) and given that BDNF seems to stimulate somatostatin synthesis (Rage et al, 1999), a decrease in BDNF due to a stress stimulus could result in a decrease in somatostatin mRNA, as observed in ISH experiments following stress (Arancibia et al, 2000 b ). If this decrease in the messenger results in diminished release, this effect might arise from activation of ultra-short feedback, which might be involved in the somatostatin regulation (Epelbaum et al, 1986).…”

“…The increase in somatostatin mRNA, as estimated by radioactive ISH, could help to explain the peak of somatostatin release precociously induced by stress application (Benyassi et al, 1993). In contrast, the decrease in the number of cells expressing the messenger detected with DIG-labeled probe could be a consequence of somatostatin ultrashort feed-back mechanisms (Epelbaum et al, 1986) through autoreceptors located on the PeV nucleus itself (Helboe et al, 1998), which would be activated by the stress stimulus.…”