WITHDRAWN: Sex differences in glucocorticoids-induced anabolic effects on energy balance.

This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been withdrawn at the request of the editor and publisher. The publisher regrets that an error occurred which led to the premature publication of this paper. This error bears no reflection on the article or its authors. The publisher apologizes to the authors and the readers for this unfortunate error.

The Increase in Signaling by Kisspeptin Neurons in the Preoptic Area and Associated Changes in Clock Gene Expression That Trigger the LH Surge in Female Rats Are Dependent on the Facilitatory Action of a Noradrenaline Input.

In rodents, kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) of the preoptic area are considered to provide a major stimulatory input to the GnRH neuronal network that is responsible for triggering the preovulatory LH surge. Noradrenaline (NA) is one of the main modulators of GnRH release, and NA fibers are found in close apposition to kisspeptin neurons in the RP3V. Our objective was to interrogate the role of NA signaling in the kisspeptin control of GnRH secretion during the estradiol induced LH surge in ovariectomized rats, using prazosin, an α1-adrenergic receptor antagonist. In control rats, the estradiol-induced LH surge at 17 hours was associated with a significant increase in GnRH and kisspeptin content in the median eminence with the increase in kisspeptin preceding that of GnRH and LH. Prazosin, administered 5 and 3 hours prior to the predicted time of the LH surge truncated the LH surge and abolished the rise in GnRH and kisspeptin in the median eminence. In the preoptic area, prazosin blocked the increases in Kiss1 gene expression and kisspeptin content in association with a disruption in the expression of the clock genes, Per1 and Bmal1. Together these findings demonstrate for the first time that NA modulates kisspeptin synthesis in the RP3V through the activation of α1-adrenergic receptors prior to the initiation of the LH surge and indicate a potential role of α1-adrenergic signaling in the circadian-controlled pathway timing of the preovulatory LH surge.

Release of norepinephrine in the preoptic area activates anteroventral periventricular nucleus neurons and stimulates the surge of luteinizing hormone.

The role of norepinephrine (NE) in regulation of LH is still controversial. We investigated the role played by NE in the positive feedback of estradiol and progesterone. Ovarian-steroid control over NE release in the preoptic area (POA) was determined using microdialysis. Compared with ovariectomized (OVX) rats, estradiol-treated OVX (OVX+E) rats displayed lower release of NE in the morning but increased release coincident with the afternoon surge of LH. OVX rats treated with estradiol and progesterone (OVX+EP) exhibited markedly greater NE release than OVX+E rats, and amplification of the LH surge. The effect of NE on LH secretion was confirmed using reverse microdialysis. The LH surge and c-Fos expression in anteroventral periventricular nucleus neurons were significantly increased in OVX+E rats dialyzed with 100 nm NE in the POA. After Fluoro-Gold injection in the POA, c-Fos expression in Fluoro-Gold/tyrosine hydroxylase-immunoreactive neurons increased during the afternoon in the A2 of both OVX+E and OVX+EP rats, in the locus coeruleus (LC) of OVX+EP rats, but was unchanged in the A1. The selective lesion of LC terminals, by intracerebroventricular N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, reduced the surge of LH in OVX+EP but not in OVX+E rats. Thus, estradiol and progesterone activate A2 and LC neurons, respectively, and this is associated with the increased release of NE in the POA and the magnitude of the LH surge. NE stimulates LH secretion, at least in part, through activation of anteroventral periventricular neurons. These findings contribute to elucidation of the role played by NE during the positive feedback of ovarian steroids.

Locus coeruleus mediates cold stress-induced polycystic ovary in rats.

Previous reports about the rat ovary have shown that cold stress promotes ovarian morphological alterations related to a polycystic ovary (PCO) condition through activation of the ovarian sympathetic nerves. Because the noradrenergic nucleus locus coeruleus (LC) is activated by cold stress and synaptically connected to the preganglionic cell bodies of the ovarian sympathetic pathway, this study aimed to evaluate the LC's role in cold stress-induced PCO in rats. Ovarian morphology and endocrine and sympathetic functions were evaluated after 8 wk of chronic intermittent cold stress (4 C, 3 h/d) in rats with or without LC lesion. The effect of acute and chronic cold stress upon the LC neuron activity was confirmed by Fos protein expression in tyrosine hydroxylase-immunoreactive neurons. Cold stress induced the formation of follicular cysts, type III follicles, and follicles with hyperthecosis alongside increased plasma estradiol and testosterone levels, irregular estrous cyclicity, and reduced ovulation. Considering estradiol release in vitro, cold stress potentiated the ovarian response to human chorionic gonadotropin. Ovarian norepinephrine (NE) was not altered after 8 wk of stress. However, LC lesion reduced NE activity in the ovary of cold-stressed rats, but not in controls, and prevented all the cold stress effects evaluated. Cold stress increased the number of Fos/tyrosine hydroxylase-immunoreactive neurons in the LC, but this effect was more pronounced for acute stress as compared with chronic stress. These results show that cold stress promotes PCO in rats, which apparently depends on ovarian NE activity that, under this condition, is regulated by the noradrenergic nucleus LC.

Bone healing in surgically created defects treated with either bioactive glass particles, a calcium sulfate barrier, or a combination of both materials. A histological and histometric study in rat tibias.

OBJECTIVE: The purpose of this study was to histologically analyze the influence of bioactive glass and/or a calcium sulfate barrier on bone healing in surgically created defects in rat tibias. MATERIAL AND METHODS: Sixty-four rats were divided into 4 groups: C (control), CS (calcium sulfate), BG (bioactive glass), and BG/CS (bioactive glass/calcium sulfate). A surgical defect was created in the tibia of each animal. In Group CS, a calcium sulfate barrier was placed to cover the defect. In Group BG the defect was filled with bioactive glass. In Group BG/CS, it was filled with bioactive glass and protected by a barrier of calcium sulfate. Animals were sacrificed at 10 or 30 days post-operative. The formation of new bone in the cortical area of the defect was evaluated histomorphometrically. RESULTS: At 10 days post-operative, Group C presented significantly more bone formation than Groups CS, BG, or BG/CS. No statistically significant differences were found between the experimental groups. At 30 days post-operative, Group C demonstrated significantly more bone formation than the experimental groups. Groups CS and BG/CS showed significantly more bone formation than Group BG. No statistically significant differences were found between Group CS and BG/CS. CONCLUSIONS: (a) the control groups had significantly more bone formation than the experimental groups; (b) at 10 days post-operative, no significant differences were found between any of the experimental groups; and (c) at 30 days post-operative, the groups with a calcium sulfate barrier had significantly more bone formation than the group that used bioactive glass only.

Healing of dehiscence defects following root surface demineralization with tetracycline: a histologic study in monkeys.

BACKGROUND: The purpose of this study was to histologically evaluate the healing of experimental dehiscence defects after surface demineralization with tetracycline hydrochloride. METHODS: Six adult male monkeys (Cebus apella) were used in this study. Dehiscence defects were surgically created on the buccal aspect of the mandibular lateral incisors in all animals. The root surfaces were debrided and planed. In a split-mouth design, a 10% tetracycline hydrochloride solution was applied to one tooth for 4 minutes (T group), followed by irrigation with saline. The contralateral tooth served as a control (C group). The flaps were repositioned and sutured. The animals were sacrificed at 6 months postoperatively and histological sections were processed. Computer-assisted histomorphometric analysis was used to evaluate the formation of new cementum, new bone, new connective tissue attachment, and length of the epithelium (junctional and sulcular). RESULTS: Bone regeneration was similar in both groups (1.5 +/- 0.3 mm for the T group and 1.5 +/- 0.6 mm for the C group). The C group showed more new cementum than the T group (2.3 +/- 0.3 mm versus 2.2 +/- 0.3 mm) as well as a longer epithelium (1.0 +/- 0.3 mm versus 0.9 +/- 0.2 mm). The T group presented more new connective tissue attachment (3.1 +/- 0.2 mm) than the C group (2.9 +/- 0.6 mm). However, no statistically significant differences were detected between the two groups. CONCLUSIONS: The amount of new attachment was similar in both groups. Root conditioning with 10% tetracycline solution did not produce any additional new attachment in comparison to the controls.