The neurotransmitter gamma-aminobutyric acid (GABA) appears to be involved in the control of gonadotropin secretion. These studies were conducted 1) to evaluate the effect of GABAergic drugs on in vitro LHRH secretion and 2) to characterize the role of different types of GABA receptors (the GABA-A and GABA-B subtypes) in these actions. Arcuate nuclei-median eminence fragments were incubated in vitro, and the release of LHRH, prostaglandin E2 (PGE2), arginine vasopressin, and oxytocin was measured by RIA. Both GABA and muscimol at different concentrations induced an increase in LHRH release, but did not affect the release of arginine vasopressin and oxytocin. This stimulatory effect was blocked by the specific GABA antagonist bicuculline, suggesting the involvement of GABA-A type receptors. Muscimol-stimulated LHRH release was not affected by the presence of phentolamine, suggesting that the stimulatory effect of GABA-A receptors on LHRH release is not mediated by interactions with the noradrenergic system. PGE2 has been shown to be a potent secretagogue of LHRH from the median eminence in vitro, and in this model the stimulatory effect of PGE2 was enhanced by muscimol. Baclofen, a specific GABA-B type receptor agonist, had no effect on basal LHRH release, but completely suppressed naloxone-stimulated LHRH and PGE2 secretion. The inhibitory effect of baclofen was blocked by the presence of 5-aminovalerate, a drug that has been shown to block the inhibitory effect of baclofen on NE release from noradrenergic terminals. This suggests the possibility that GABA-B receptors interacting with noradrenergic terminals may be responsible for the inhibitory effect of baclofen on naloxone stimulation. This study uncovered both stimulatory and inhibitory effects of GABA on LHRH release after activation of GABA-A or GABA-B receptors, respectively. Further, the data show possible relationships among the GABAergic, endogenous opiate peptide, and noradrenergic systems in the control of LHRH release from the hypothalamus.

Neuropeptides are defined chemical messengers produced by the brain to modulate its own activity and also to regulate the function of every organ system. These neuropeptides can be viewed as coded chemical signals produced by the brain and secreted into the blood or into other fluids, such as the cerebrospinal fluid, to be transported and to act at a distant site. The signals arrive to the target organ or sometimes to an intermediary station, such as the pituitary gland, where they are decoded, transformed into a more powerful signal, and sent again through the general circulation to reach their final target. Our work has characterized the episodic or pulsatile pattern of secretion of a number of peptide hormones produced by the brain or the pituitary gland and analyzed the brain mechanisms involved in the generation of such a pulsatile pattern of hormone secretion. Molecular biology approaches have provided information on the synthesis, processing, and secretion of these brain messengers. In addition, using computer-assisted perifusion systems, we have been able to reproduce in vitro some of the signals produced by the brain and are currently trying to decode the message carried by those signals, as well as determining the intracellular messengers involved in the signal process. The importance of the neuropeptides and of the messages carried by the pulsatile signal is underlined by experiments in which animals treated with a neurotoxin were rendered infertile.(ABSTRACT TRUNCATED AT 250 WORDS)

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. The National Institute of Environmental Health Sciences (NIEHS) and Brogan & Partners are collaborating with JSTOR to digitize, preserve and extend access to Environmental Health Perspectives.Neuropeptides are defined chemical messengers produced by the brain to modulate its own activity and also to regulate the function of every organ system. These neuropeptides can be viewed as coded chemical signals produced by the brain and secreted into the blood or into other fluids, such as the cerebrospinal fluid, to be transported and to act at a distant site. The signals arrive to the target organ or sometimes to an intermediary station, such as the pituitary gland, where they are decoded, transformed into a more powerful signal, and sent again through the general circulation to reach their final target. Our work has characterized the episodic or pulsatile pattern of secretion of a number of peptide hormones produced by the brain or the pituitary gland and analyzed the brain mechanisms involved in the generation of such a pulsatile pattern of hormone secretion. Molecular biology approaches have provided information on the synthesis, processing, and secretion of these brain messengers. In addition, using computer-assisted perifusion systems, we have been able to reproduce in vitro some of the signals produced by the brain and are currently trying to decode the message carried by those signals, as well as determining the intracellular messengers involved in the signal process. The importance of the neuropeptides and of the messages carried by the pulsatile signal is underlined by experiments in which animals treated with a neurotoxin were rendered infertile. The neurotoxin affects a number of neuronal systems within the brain and destroys or impairs the activity of many peptidergic neurons in areas of the brain related to regulation of reproductive functions. This work has also established that the pulsatile hormone signals seen in normal animals are either absent or grossly impaired in the infertile animals treated with the neurotoxin. Studies of pulsatile hormone secretion are, therefore, very useful peripheral markers for the evaluation of changes in cerebral function. In addition, very valuable diagnostic and therapeutic applications can be derived from the study of pulsatility patterns of neuropeptide secretion. compartments, the brain can effectively send chemical signals to modify the activity of the different organs or cell systems under its influence. This mechanism of transformation of an electrical impulse into a defined chemical signal is a classical example of signal transduction. As a result of the transduction of the signal, many well-defined substances are secreted into th...