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Estrogen modifies stress-elicited response of catecholamine biosynthetic enzyme genes and cardiovascular system in ovariectomized female rats
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Abstracts / Frontiers in Neuroendocrinology 27 (2006) 91–94
Estrogen modifies stress-elicited response of catecholamine biosynthetic enzyme genes and cardiovascular system in ovariectomized female rats Esther Louise Sabban, Lidia Serova New York Medical College, Valhalla, New York, USA Estrogen is likely involved in the gender-specific differences in coping with stress. Activation of catecholamine (CA) biosynthetic enzyme gene expression in central and peripheral CA systems plays a key role in response to stress and in regulation of the cardiovascular system. Here, we examined whether estradiol can modulate: response of hypothalamic–pituitary–adrenal axis (HPA); gene expression of enzymes related to CA biosynthesis in several noradrenergic locations; tetrahydrobiopterin (BH4) concentration; and blood pressure (BP), in response to single immobilization stress (IMO) of ovariectomized female rats. Rats were injected with 25 lg/kg estradiol benzoate (EB) or sesame oil once daily for 16 days and subsequently exposed to 2 h of IMO. The IMO-triggered elevation in plasma ACTH was lessened in EB-pretreated animals. However, estradiol did not alter the IMO-elicited rise of tyrosine hydroxylase mRNA levels in adrenal medulla (AM) and in the nucleus of solitary tract (NTS) compared with controls. The response of GTP cyclohydrolase I (GTPCH) mRNA in AM to IMO was also similar in both groups. Several responses to IMO in EB-treated rats were reversed. Instead of IMO-elicited elevation in dopamine b-hydroxylase mRNA levels in the locus coeruleus, GTPCH mRNA and BH4 levels in the NTS, they were reduced by IMO. In a parallel experiment, BP was monitored during restraint stress. The elevation of BP in response to single or repeated restraint stress was sustained during 2 h in controls and reduced after 70 min stress in EB-treated rats. One month after withdrawal of EB treatment, the BP response to restraint was similar to that of rats which never received EB. Our results indicate that estrogen can modulate stressinduced changes in HPA axis, gene expression for CA biosynthetic enzymes in central and peripheral noradrenergic systems and blood pressure. (Supported by 0130102N from American Heart Association and NS28869 from NIH.) doi:10.1016/j.yfrne.2006.03.207
Pituitary adenylate cyclase-activating polypeptide (PACAP) and gonadotropin subunit gene expression in the fetal and newborn pituitary Stephen J. Winters, Joseph P. Moore Division of Endocrinology, Metabolism and Diabetes, University of Louisville, USA In vitro studies reveal that PACAP differentially regulates the expression of the gonadotropins by stimulating a-subunit and lengthening LHb transcripts but decreasing FSHb mRNA levels by stimulating follistatin transcrip-
tion. While PACAP has been proposed as a hypophysiotropic peptide, we found a high level of PACAP expression in the fetal rat pituitary implying a paracrine/ autocrine function. The present studies were performed to characterize the pituitary expression of PACAP during the perinatal period, and to examine its expression in relation to gonadotropin subunit and follistatin gene expression at birth. Using laser capture micro-dissection and RT-PCR, PACAP mRNA was detected within the pituitary as early as embryonic-day (E) 11. Utilizing RNA isolated from whole pituitaries, real-time PCR revealed a very high level of PACAP mRNA at E19 at which time the ratio of LHb to FSHb mRNAs was 125:1. PACAP mRNA declined by 90%, and follistatin-288 mRNA decreased by 98% within 1 day after parturition (post-natal day 1; PN1), while FSHb mRNA rose 20-fold and LH-b mRNA rose 3-fold; i.e., the ratio of LHb to FSHb mRNA fell to 26:1. GnRH-R mRNA also increased 5-fold from E19 to PN1. To further evaluate the relationship between PACAP and FSHb expression in the fetus and newborn, we examined these mRNAs in wild-type and PACAP-deficient (KO) mice. Preliminary results suggest that PACAP expression in the normal mouse pituitary follows a similar developmental pattern to the rat, with lower levels at PN1 than E20. Furthermore, FSHb mRNA levels are higher in pituitaries from embryonic and early post-natal PACAPKO mice than in PACAP-expressing littermates. These data support the hypothesis that high levels of pituitary PACAP restrain FSH as well as GnRH-R synthesis in the fetal pituitary by stimulating follistatin 288, and suggest that a decline in pituitary PACAP at birth is an important event in the neonatal activation of gonadotrophs and thereby gonadal development in rodents. doi:10.1016/j.yfrne.2006.03.208
Neurochemical phenotype of LGR7-positive neurons in mouse brain? Studies in the LGR7-knock-out/LacZ-knockin mouse L.G. Piccenna a, P.-J. Shen a, S. Ma a, R.A.D. Bathgate a, S. Mosselmann b, A.L. Gundlach a a Howard Florey Institute, The University of Melbourne, Vic. 3010, Australia b Pharmacology, NV Organon, 5340BH Oss, The Netherlands Previous studies of rat brain have revealed that the relaxin receptor, leucine-rich repeat-containing G proteincoupled receptor 7 (LGR7), is widely distributed in cortical and subcortical areas, while relaxin is produced by a limited population of neurons in olfactory, cortical, and hypothalamic regions. In research to learn more about the role of relaxin-LGR7 signalling in the brain, we are investigating the neurochemical and behavioural phenotype of LGR7-knock-out (KO)/LacZ-knock-in mice [Mol. Cell.
Abstracts / Frontiers in Neuroendocrinology 27 (2006) 91–94
Estrogen modifies stress-elicited response of catecholamine biosynthetic enzyme genes and cardiovascular system in ovariectomized female rats Esther Louise Sabban, Lidia Serova New York Medical College, Valhalla, New York, USA Estrogen is likely involved in the gender-specific differences in coping with stress. Activation of catecholamine (CA) biosynthetic enzyme gene expression in central and peripheral CA systems plays a key role in response to stress and in regulation of the cardiovascular system. Here, we examined whether estradiol can modulate: response of hypothalamic–pituitary–adrenal axis (HPA); gene expression of enzymes related to CA biosynthesis in several noradrenergic locations; tetrahydrobiopterin (BH4) concentration; and blood pressure (BP), in response to single immobilization stress (IMO) of ovariectomized female rats. Rats were injected with 25 lg/kg estradiol benzoate (EB) or sesame oil once daily for 16 days and subsequently exposed to 2 h of IMO. The IMO-triggered elevation in plasma ACTH was lessened in EB-pretreated animals. However, estradiol did not alter the IMO-elicited rise of tyrosine hydroxylase mRNA levels in adrenal medulla (AM) and in the nucleus of solitary tract (NTS) compared with controls. The response of GTP cyclohydrolase I (GTPCH) mRNA in AM to IMO was also similar in both groups. Several responses to IMO in EB-treated rats were reversed. Instead of IMO-elicited elevation in dopamine b-hydroxylase mRNA levels in the locus coeruleus, GTPCH mRNA and BH4 levels in the NTS, they were reduced by IMO. In a parallel experiment, BP was monitored during restraint stress. The elevation of BP in response to single or repeated restraint stress was sustained during 2 h in controls and reduced after 70 min stress in EB-treated rats. One month after withdrawal of EB treatment, the BP response to restraint was similar to that of rats which never received EB. Our results indicate that estrogen can modulate stressinduced changes in HPA axis, gene expression for CA biosynthetic enzymes in central and peripheral noradrenergic systems and blood pressure. (Supported by 0130102N from American Heart Association and NS28869 from NIH.) doi:10.1016/j.yfrne.2006.03.207
Pituitary adenylate cyclase-activating polypeptide (PACAP) and gonadotropin subunit gene expression in the fetal and newborn pituitary Stephen J. Winters, Joseph P. Moore Division of Endocrinology, Metabolism and Diabetes, University of Louisville, USA In vitro studies reveal that PACAP differentially regulates the expression of the gonadotropins by stimulating a-subunit and lengthening LHb transcripts but decreasing FSHb mRNA levels by stimulating follistatin transcrip-
tion. While PACAP has been proposed as a hypophysiotropic peptide, we found a high level of PACAP expression in the fetal rat pituitary implying a paracrine/ autocrine function. The present studies were performed to characterize the pituitary expression of PACAP during the perinatal period, and to examine its expression in relation to gonadotropin subunit and follistatin gene expression at birth. Using laser capture micro-dissection and RT-PCR, PACAP mRNA was detected within the pituitary as early as embryonic-day (E) 11. Utilizing RNA isolated from whole pituitaries, real-time PCR revealed a very high level of PACAP mRNA at E19 at which time the ratio of LHb to FSHb mRNAs was 125:1. PACAP mRNA declined by 90%, and follistatin-288 mRNA decreased by 98% within 1 day after parturition (post-natal day 1; PN1), while FSHb mRNA rose 20-fold and LH-b mRNA rose 3-fold; i.e., the ratio of LHb to FSHb mRNA fell to 26:1. GnRH-R mRNA also increased 5-fold from E19 to PN1. To further evaluate the relationship between PACAP and FSHb expression in the fetus and newborn, we examined these mRNAs in wild-type and PACAP-deficient (KO) mice. Preliminary results suggest that PACAP expression in the normal mouse pituitary follows a similar developmental pattern to the rat, with lower levels at PN1 than E20. Furthermore, FSHb mRNA levels are higher in pituitaries from embryonic and early post-natal PACAPKO mice than in PACAP-expressing littermates. These data support the hypothesis that high levels of pituitary PACAP restrain FSH as well as GnRH-R synthesis in the fetal pituitary by stimulating follistatin 288, and suggest that a decline in pituitary PACAP at birth is an important event in the neonatal activation of gonadotrophs and thereby gonadal development in rodents. doi:10.1016/j.yfrne.2006.03.208
Neurochemical phenotype of LGR7-positive neurons in mouse brain? Studies in the LGR7-knock-out/LacZ-knockin mouse L.G. Piccenna a, P.-J. Shen a, S. Ma a, R.A.D. Bathgate a, S. Mosselmann b, A.L. Gundlach a a Howard Florey Institute, The University of Melbourne, Vic. 3010, Australia b Pharmacology, NV Organon, 5340BH Oss, The Netherlands Previous studies of rat brain have revealed that the relaxin receptor, leucine-rich repeat-containing G proteincoupled receptor 7 (LGR7), is widely distributed in cortical and subcortical areas, while relaxin is produced by a limited population of neurons in olfactory, cortical, and hypothalamic regions. In research to learn more about the role of relaxin-LGR7 signalling in the brain, we are investigating the neurochemical and behavioural phenotype of LGR7-knock-out (KO)/LacZ-knock-in mice [Mol. Cell.