Electrical Stimulation of Specific Brainstem Nuclei Suppresses Growth Hormone‐Releasing Hormone‐Induced Growth Hormone Secretion in the Pentobarbital Anaesthetized Rat

Abstract

To clarify the neural mechanism related to suppression of growth hormone (GH) secretion, biphasic electrical stimulation was delivered into several brainstem nuclei in the pentobarbital anaesthetized rat. A concentric bipolar stimulating electrode was implanted chronically one week prior to the electrical stimulation. Ninety min before the electrical stimulation, the rats were anaesthetized by ip injection of pentobarbital and a silastic cannula was inserted into the right atrium for blood sampling. Blood samples were withdrawn five times (0, 10, 20, 30 and 60 min) during the experiment. Electrical stimulation was delivered for 10 min just after the first blood sampling. One min after the onset of the stimulation, human GH-releasing hormone was injected iv to induce GH secretion. Electrical stimulation of several brainstem nuclei, i.e. the locus coeruleus, the rostra1 portion of the nucleus tractus solitarius and the lateral reticular nucleus suppressed GH secretion and the central gray of the pons showed a tendency for the suppression of GH secretion. On the other hand, electrical stimulation of the parabrachial nucleus and the caudal portion of the nucleus tractus solitarius did not suppress GH secretion. These suppressions were nullified by prior electrolytic lesioning of the hypothalamic periventricular nucleus where the major cell bodies of somatostatin immunoreactive fibres in the median eminence originate. These results indicate that electrical stimulation of several brainstem nuclei excites somatostatin neurons in the periventricular nucleus which are responsible for the suppression of GH secretion.The control of growth hormone (GH) secretion is accomplished by two hypothalamic peptides, GH-releasing hormone (GHRH) and somatostatin (SRIF) (1, 2). The suppression of GH secretion was exerted by SRIF, which is released from the median eminence (ME) into the hypophyseal portal blood (3). The SRIF immunoreactive cell bodies and fibres are distributed throughout the CNS (4, 5). However, retrograde tracing studies suggest that the SRIF immunoreactive fibres in the M E originate in the hypothalamic periventricular nucleus (Pe) (6, 7). On the other hand, the neural circuitry which controls SRIF neurons is not yet understood.Past experiments have revealed the topography of the CNS in which several loci suppress human GHRH-(hGHRH) induced G H secretion by electrical stimulation (8-10). Electrical stimulation of the Pe, which directly activates SRIF neurons, suppresses hGHRH-induced G H secretion (8). Electrical stimulation of the other brain structures, i.e. the lateral septum (9), the organum vasculosum of the lamina terminalis (8), the bed nucleus of the stria terminalis (9), the lateral hypothalamic area (8), the medial amygdala (9), the ventral premammillary nucleus (8) and the midbrain central gray (lo), suppresses hGHRH-induced GH secretion. As these suppressions are abolished by prior lesioning of the Pe, it is indicated that electrical stimulations of these nuclei cause the excitation of SRIF neuron...

Alpha-1-Noradrenergic Inhibition of Growth Hormone Secretion Is Mediated through the Paraventricular Hypothalamic Nucleus in Male Rats

“…In the rat, pretreatment with anti-SRIF antisera was re ported to abolish the action of methoxamine [5]. In addi tion, acute electrical stimulation of the LC suppresses GH secretion induced by GH-releasing hormone in pentobar bital-anesthetized rats provided the periventricular nu cleus is intact [6],…”

Enhanced Response of Growth Hormone to Growth Hormone‐Releasing Hormone and a Decreased Content of Hypothalamic Somatostatin in a Stress‐Induced Rat Model of Depression

“…Because SRIF neurons are associated functionally with Lesch et al (17,18). reported attenuated release of GH in response to hGHRH in depressed patients, while Krishnan noradrenergic neurons (29), hypoactivity of SRIF neurons might be related to the dysfunction of noradrenergic neurons. et al (19).…”

Activation of Locus Coeruleus Somatostatin Receptors Induces an Increase of Growth Hormone Release in Male Rats

“…In the case of growth hormone (GB) secretion. acute electrical stimulation of the LC suppresses OH releasinghormone (GHRH) induced OH secretion in pentobarbital anaestheUad rats (2). Conversely.…”

“…The negative inftuence ofLC neurons over the amplitude of OH pulses is probably relayed by somatostatin (SRIH) neurons of the periventricular hypothalamic. : area (PeV), since lesion of that structure suppresses the hormonal response to LC stimulation (2).…”