| Abstract: |
Summary And ConclusionCalcitonin gene related peptide (CGRP) is a 37 amino acid neuropeptide synthesized primarily in dorsal root ganglia (DRG) and distributed widely in the perivascular nerves, suggesting that this peptide may play a role in the regulation of peripheral vascular tone. Since female sex steroid hormones have been implicated in the regulation of peripheral vascular tone during pregnancy, we postulated that they may alter the concentration of CGRP in the circulation and thus modulate the increased blood flow observed during pregnancy.This work was carried out to evaluate the changes in serum levels of CGRP in pregnant, ovariectomized, and ovariectomized female sex steroids hormones (estradiol and progesterone)-treated healthy adult female rats.A total number of 80 healthy adult albino rats (72 female rats and 8 male rats) weighting 180-200 grams body weight were used in this study. All animals were bred in the animal house under hygienic conditions and kept on the diet which consisted of mixed commercial rat laboratory chow and supplied in separate clean containers and had free access to water.The male rats were used for induction of pregnancy. The first day of pregnancy was determined by examination of vaginal smear of females the next morning after mating with male. The presence of sperms indicated the first day of gestation.Female rats were divided into 3 large groups:The first group was the control group (non-pregnant non-ovariectomized) rats (n = 6 rats).The second group was the Ovariectomized group (n = 42 rats).The third group was the timed pregnant group (n= 24 rats).• All ovariectomized rats were left for 7 days after the operation for healing and acclimatization. Then they were divided into 4 main groups:1-The first group: (Ovariectomized Sesame oil-treated group = vehicle-treated control group):This group consisted of 6 rats, each rat received 0.2 ml sesame oil S.C. twice daily for 3 days.2-The second group: (Estradiol-treated group):This group consisted of 12 rats, which were divided into 2 subgroups:☻the first subgroup consisted of 6 rats, each rat was treated S.C. with 17β-estradiol in a dose of 2.5 μg (small dose) in 0.2 ml sesame oil / injection twice daily for 3 days.☻the second subgroup consisted of 6 rats, each rat was treated S.C. with 17β-estradiol in a dose of 5 μg (large dose) in 0.2 ml sesame oil / injection twice daily for 3 days.3-The third group: (Progesterone-treated group):This group consisted of 12 rats, which were divided into 2 subgroups:☻the first subgroup consisted of 6 rats, each rat was treated S.C. with progesterone in a dose of 2 mg (small dose) in 0.2 ml sesame oil / injection twice daily for 3 days.☻the second subgroup consisted of 6 rats, each rat was treated S.C. with progesterone in a dose of 4 mg (large dose) in 0.2 ml sesame oil / injection twice daily for 3 days.4-The fourth group: (Combined estradiol and Progesterone-treated group):This group consisted of 12 rats, which were divided into 2 subgroups:☻the first subgroup consisted of 6 rats, in which each rat was injected S.C. with a small dose of the combination of both 17B-estradiol in a dose of 2.5µg / injection and progesterone in a dose of 2 mg / injection twice daily for three days.☻the second subgroup consisted of 6 rats, in which each rat was injected S.C. with a large dose of the combination of both 17B-estradiol in a dose of 5µg/ injection and progesterone in a dose of 4 mg / injection twice daily for three days.• The timed pregnant animals were divided into for 4 equal subgroups (n = 6 in each group) on different stages of gestation, early pregnant rats (on day 7 of gestation), late pregnant rats (on day 19 of gestation), pregnant rats at the expected day of parturition, and pregnant rats after labor (2 day post-partum).The animals were sacrificed at 9–11 A.M. and blood was collected then the serum was separated. The levels of CGRP, estrogen, and progesterone were estimated in all studied groups but the prolactin level was estimated in control rats (non-pregnant non-ovariectomized) and all pregnant rats during gestation (early and late), at the expected day of parturition and after delivery (2 days post partum).The results of the present study revealed that:• The concentrations of CGRP in the circulation were significantly elevated throughout gestation with higher levels obtained near to term and these levels declined sharply at the expected day of parturition and 2 days postpartum.• CGRP concentrations were significantly decreased in the blood of ovariectomized rats compared to the control (non-pregnant, non-ovariectomized) rats.• In non pregnant ovariectomized rats, three days treatment either with estrogen or progesterone, either alone or in combination, significantly elevated the blood CGRP concentrations compared to the vehicle (sesame oil)-administrated ovariectomized rats. Furthermore, the circulatory concentrations of CGRP in the combined estrogen and progesterone treated rats were significantly greater than those of either estrogen, or progesterone administrated rats.• The circulatory concentrations of CGRP in pregnant rats at day 19 of gestation were greater than those achieved with the combined estrogen and progesterone administration in ovariectomized rats.• Significant positive correlations were found between the circulating levels of CGRP, estradiol and progesterone in all studied groups.• Peripheral progesterone concentrations are high during gestation and declined before parturition in pregnant rats while estrogen concentrations showed a progressive increase throughout gestation to reach a very high level just before parturition.• The concentrations of prolactin in the circulation were significantly elevated in pregnant rats near to term (at the expected day of parturition) and there was a significant negative correlation between circulating CGRP and prolactin levels at that time.Conclusion:It could be concluded that estrogen and progesterone are important regulators of serum CGRP levels. Hence, the female sex steroid hormones induced changes in CGRP levels may play an important role in:• The vasoprotective effects in young adult females in the child bearing period or in those taking contraceptive pills.• The cardiovascular protection in postmenopausal women on hormone replacement therapy thus, the decrease in cardiovascular protection in postmenopausal women is likely to be due to reduction in CGRP synthesis and/or release in peripheral tissues as a result of the hormone depletion (decrease in circulating level of estrogens and progesterone).• The vascular adaptation as well as vasodilatation that occur during pregnancy and so protect against the occurrence of preeclampsia.• the uterine smooth muscle relaxation (uterine quiescence) that required for successful pregnancy and hence, the prevention of preterm labor.Further detailed studies are required to fully assess the contributing factor (s) other than sex steroid hormones which may be involved in the process of CGRP synthesis and release during pregnancy and to determine the mechanism (s) by which female sex steroid hormone can modify this process.
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