+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found

      Role of the Progesterone Receptor in Restrained Glutamic Acid Decarboxylase Gene Expression in the Hypothalamus during the Preovulatory Luteinizing Hormone Surge

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Previous work by our laboratory demonstrated that activation of the progesterone receptor through exogenous administration of progesterone suppressed glutamic acid decarboxylase-67 (GAD<sub>67</sub>) mRNA in the hypothalamus of the estrogen-primed ovariectomized rat. Since GAD<sub>67</sub> is the major synthetic enzyme for the inhibitory transmitter, γ-aminobutyric acid, the finding raised the possibility that the endogenous activation of the progesterone receptor may act to restrain GAD<sub>67</sub> expression during the natural preovulatory gonadotropin surge during proestrus in the rat, thereby allowing GnRH secretion and the resultant LH surge. To test this hypothesis, the progesterone receptor antagonist, RU486, was administered to regularly cycling proestrous rats and the effect on GAD<sub>67</sub> and GAD<sub>65</sub> mRNA levels in the preoptic area (POA) and medial basal hypothalamus (MBH) was examined. Serum luteinizing hormone (LH) levels were also examined in order to identify correlations between changes in POA and MBH GAD levels and production of the LH surge. GAD<sub>67</sub> mRNA levels in the POA were increased in the cycling rat during proestrus at 18.00 h at the peak and just preceding the termination of the LH surge. There was no change in GAD<sub>67</sub> mRNA levels in the MBH, and GAD<sub>65</sub> expression was also unchanged during proestrus in the POA and MBH. Treatment with the antiprogestin RU486 resulted in an increase in GAD<sub>67</sub> mRNA levels at 12.00 and 14.00 h in the POA, and in the MBH at 14.00, 16.00, and 18.00 h during proestrus, effects which preceded and correlated with the attenuated LH surge in RU486-treated rats at 18.00 h. GAD<sub>65</sub> mRNA levels were also elevated by RU486 at 14.00 and 16.00 h in the POA, and at 14.00 h in the MBH during proestrus. These findings suggest that the progesterone receptor plays a role in restraining GAD expression in the hypothalamus during proestrus, and that this effect may be important for the production of the GnRH and LH surge.

          Related collections

          Most cited references 5

          • Record: found
          • Abstract: found
          • Article: not found

          Changes in the control of gonadotrophin secretion by neurotransmitters during sexual development in rats.

          Gonadotrophin hormone releasing hormone (GnRH) is the primary messenger involved in sexual maturation and the onset of puberty. The activity of these neurons are controlled by several neurotransmitters systems. The onset of puberty implies changes from a prepubertal type of gonadotrophin secretion, characterized by a low activity of GnRH neurons, to an adult pattern of secretion with phasic and synchronous activation of GnRH neurons resulting in an increase in the amplitute and frequency of GnRH pulses. Neurotransmitter systems are involved in these changes of GnRH secretion during the onset of puberty by quantitative and qualitative modifications in the effect on GnRH secretion. Serotonin (5-HT), GABA and catecholamines (CA) have qualitative differences in the effects on GnRH and LH secretion in early prepubertal than in late prepubertal and adult female rats. The administration of 5-hydroxytryptophan a precursor of serotonin (5-HT) which increases 5-HT hypothalamic levels induces GnRH and LH release in early prepubertal female rats, these effects dissapear in late prepubertal stage having an inhibitory action in adult female rats. GABAergic system also stimulates GnRH and LH secretion in early prepubertal female rats and has an inhibitory action on this axis in late prepubertal period and in adult female rats. On the contrary the inhibition of catecholamines synthesis by alpha-methyl-p-tyrosine induced an increase of LH secretion in early prepubertal female rats and inhibitory effect in late prepubertal and adult stage. These effects indicate tha CA has an inhibitory effects on GnRH-LH secretion in early prepubertal female rats changing to an stimulatory action in the late puberty and adult rats. These qualitative modifications were observed only in female rats and are probably connected with the hypothalamic differentiation into a female type of gonadotrophin control. Opiadergic and excitatory amino acid systems have quantitative differences on GnRH-LH secretion during prepubertal and peripubertal and adult stages. Opiates has an high inhibitory tone in early prepubertal rats that is decreasing during sexual maturation to reach puberty. On the contrary EAA increases its stimulatory activity on GnRH-LH secretion during sexual maturation by increasing the hypothalamic release of aspartate and glutamate, the excitatory amino acids involved in GnRH release, and the sensibility of NMDA receptors to these amino acids. In conclusion sexual maturation and the onset of puberty in the female rats involve qualitative and quantitative modifications in the effects of neurotrasmitters system on GnRH secretion.
            • Record: found
            • Abstract: not found
            • Article: not found

            Expression of glutamic acid decarboxylase messenger RNA in rat medial preoptic area neurones during the oestrous cycle and after ovariectomy

              • Record: found
              • Abstract: found
              • Article: not found

              Interaction between ovarian and adrenal steroids in the regulation of gonadotropin secretion.

              Recent work from our laboratory suggests that a complex interaction exists between ovarian and adrenal steroids in the regulation of preovulatory gonadotropin secretion. Ovarian estradiol serves to set the neutral trigger for the preovulatory gonadotropin surge, while progesterone from both the adrenal and the ovary serves to (1) initiate, (2) synchronize, (3) potentiate and (4) limit the preovulatory LH surge to a single day. Administration of RU486 or the progesterone synthesis inhibitor, trilostane, on proestrous morning attenuated the preovulatory LH surge. Adrenal progesterone appears to play a role in potentiating the LH surge since RU486 still effectively decreased the LH surge even in animals ovariectomized at 0800 h on proestrus. The administration of ACTH to estrogen-primed ovariectomized (ovx) immature rats caused a LH and FSH surge 6 h later, demonstrating that upon proper stimulation, the adrenal can induce gonadotropin surges. The effect was specific for ACTH, required estrogen priming, and was blocked by adrenalectomy or RU486, but not by ovariectomy. Certain corticosteroids, most notably deoxycorticosterone and triamcinolone acetonide, were found to possess "progestin-like" activity in the induction of LH and FSH surges in estrogen-primed ovx rats. In contrast, corticosterone and dexamethasone caused a preferential release of FSH, but not LH. Progesterone-induced surges of LH and FSH appear to require an intact N-methyl-D-aspartate (NMDA) neurotransmission line, since administration of the NMDA receptor antagonist, MK801, blocked the ability of progesterone to induce LH and FSH surges. Similarly, NMDA neurotransmission appears to be a critical component in the expression of the preovulatory gonadotropin surge since administration of MK801 during the critical period significantly diminished the LH and PRL surge in the cycling adult rat. FSH levels were lowered by MK801 treatment, but the effect was not statistically significant. The progesterone-induced gonadotropin surge appears to also involve mediation through NPY and catecholamine systems. Immediately preceding the onset of the LH and FSH surge in progesterone-treated estrogen-primed ovx. rats, there was a significant elevation of MBH and POA GnRH and NPY levels, which was followed by a significant fall at the onset of the LH surge. The effect of progesterone on inducing LH and FSH surges also appears to involve alpha 1 and alpha 2 adrenergic neuron activation since prazosin and yohimbine (alpha 1 and 2 blockers, respectively) but not propranolol (a beta-blocker) abolished the ability of progesterone to induce LH and FSH surges. Progesterone also caused a dose-dependent decrease in occupied nuclear estradiol receptors in the pituitary.(ABSTRACT TRUNCATED AT 400 WORDS)

                Author and article information

                S. Karger AG
                November 2002
                02 December 2002
                : 76
                : 5
                : 283-289
                Institute of Molecular Medicine and Genetics, and Department of Neurology, Neurobiology Program, Medical College of Georgia, Augusta, Ga., USA
                66628 Neuroendocrinology 2002;76:283–289
                © 2002 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 5, References: 31, Pages: 7
                Reproductive Neuroendocrinology


                Comment on this article