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Disorders in secretion or function of insulin leads to dia- betes. One of the important effects of diabetes is neuropa- thy, so pain sensitivity in diabetic patient’s decreases. On the other hand pain sensitivity was changed during estrous cycle. So the aim of present study was investigated pain sensitivity during estrous cycle in female diabetic rats. Adults’ female rats weighing about 250 g were maintained on 12 h light/dark cycle for 10–14 day prior to the experi- ments. Food and water were available ad libitum. Animal were divide to two groups, healthy and diabetic rats. Stages of estrous cycle were monitored by vaginal lavage. Pain sensitivity was evaluated by tail flick test. Tail flick test was performed for 60 min during all stages of estrous cycle. Data were analyzed by T-Student test. The level of signifi- cant was p < 0.05. Results show that pain sensitivity in diabetic group was significantly lower than healthy subject. Analgesic effect of diabetes was different during estrous cycle. It was high in metestruse and low in diestruse. Our results indicated that neurophatic effect of diabetes was different during estrous cycle. So, sex steroids can affect the neurophatic effect of diabetes (Fig. 1). doi:10.1016/j.yfrne.2006.03.300 Increased local synthesis of progesterone in the nervous system: A response to injury Michael Schumacher a , Florencia Labombarda b , Philippe Liere a , Alejandro F. De Nicola b , Rachida Guennoun a a Inserm UMR 788, Univ. Paris 11, 80, rue du Ge ´ne ´ral Leclerc, 94276 Bice ˆtre, France b Lab. Neuroendocrine Biochemistry, Univ. of Buenos Aires, Argentina With respect to the neuroprotective and neuroregenera- tive effects of steroids, attention has mainly focused on the estrogens. However, progesterone and its metabolites have recently been shown to promote neuronal survival and to play an important role in myelination during development, regeneration, and aging. The recognition of the important pleitropic effects of progesterone opens novel perspectives for the treatment of lesions and diseases of the nervous sys- tem, and it has important implications for hormone replace- ment therapies. Analysis by gas chromatography/mass spectrometry revealed that levels of progesterone and its metabolites are significantly upregulated in the spinal cord of male rats 75 h after transection injury. The steroidogenic endocrine glands may have contributed to these increases as steroids easily cross the blood–brain barrier. However, two observations pointed to an increased local synthesis of pro- gesterone in response to the lesion: (1) levels of pregneno- lone, the direct precursor of progesterone, were increased within spinal cord tissue, but not in plasma; (2) levels of ste- roids were higher in the spinal cord than in blood. All the enzymes necessary for the synthesis and metabolism of pro- gesterone are indeed expressed in the spinal cord, namely, the cytochrome P450scc, the 3b-hydroxysteroid dehydrogenase, the two isoforms of the 5a-reductase and the 3a-hydroxy- steroid oxidoreductase. We then showed that in the spinal cord of male rats deprived of their steroidogenic endocrine glands by castration and adrenalectomy, transection injury caused a rapid rise in levels of the precursor steroid pregnen- olone, followed 2 days later by an important increase in pro- gesterone. Circulating levels of the steroids were barely detectable and did not change in response to lesion. These results demonstrate that the nervous system responds to injury with an increase in the local synthesis of pregnenolone, progesterone, and its 5a-reduced metabolites, consistent with an important role of these neurosteroids in neuropro- tection and regeneration. doi:10.1016/j.yfrne.2006.03.301 Abstracts / Frontiers in Neuroendocrinology 27 (2006) 111–117 117

Increased local synthesis of progesterone in the nervous system: A response to injury

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Disorders in secretion or function of insulin leads to dia-betes. One of the important effects of diabetes is neuropa-thy, so pain sensitivity in diabetic patient’s decreases. Onthe other hand pain sensitivity was changed during estrouscycle. So the aim of present study was investigated painsensitivity during estrous cycle in female diabetic rats.Adults’ female rats weighing about 250 g were maintainedon 12 h light/dark cycle for 10–14 day prior to the experi-ments. Food and water were available ad libitum. Animalwere divide to two groups, healthy and diabetic rats. Stagesof estrous cycle were monitored by vaginal lavage. Painsensitivity was evaluated by tail flick test. Tail flick testwas performed for 60 min during all stages of estrous cycle.Data were analyzed by T-Student test. The level of signifi-cant was p < 0.05.

Results show that pain sensitivity in diabetic group wassignificantly lower than healthy subject. Analgesic effect ofdiabetes was different during estrous cycle. It was high inmetestruse and low in diestruse.

Our results indicated that neurophatic effect of diabeteswas different during estrous cycle. So, sex steroids canaffect the neurophatic effect of diabetes (Fig. 1).

doi:10.1016/j.yfrne.2006.03.300

Increased local synthesis of progesterone in the nervous

system: A response to injury

Michael Schumacher a, Florencia Labombarda b, Philippe

Liere a, Alejandro F. De Nicola b, Rachida Guennoun a

a Inserm UMR 788, Univ. Paris 11, 80, rue du General

Leclerc, 94276 Bicetre, Franceb Lab. Neuroendocrine Biochemistry, Univ. of Buenos Aires,

Argentina

With respect to the neuroprotective and neuroregenera-tive effects of steroids, attention has mainly focused on the

estrogens. However, progesterone and its metabolites haverecently been shown to promote neuronal survival and toplay an important role in myelination during development,regeneration, and aging. The recognition of the importantpleitropic effects of progesterone opens novel perspectivesfor the treatment of lesions and diseases of the nervous sys-tem, and it has important implications for hormone replace-ment therapies. Analysis by gas chromatography/massspectrometry revealed that levels of progesterone and itsmetabolites are significantly upregulated in the spinal cordof male rats 75 h after transection injury. The steroidogenicendocrine glands may have contributed to these increases assteroids easily cross the blood–brain barrier. However, twoobservations pointed to an increased local synthesis of pro-gesterone in response to the lesion: (1) levels of pregneno-lone, the direct precursor of progesterone, were increasedwithin spinal cord tissue, but not in plasma; (2) levels of ste-roids were higher in the spinal cord than in blood. All theenzymes necessary for the synthesis and metabolism of pro-gesterone are indeed expressed in the spinal cord, namely, thecytochrome P450scc, the 3b-hydroxysteroid dehydrogenase,the two isoforms of the 5a-reductase and the 3a-hydroxy-steroid oxidoreductase. We then showed that in the spinalcord of male rats deprived of their steroidogenic endocrineglands by castration and adrenalectomy, transection injurycaused a rapid rise in levels of the precursor steroid pregnen-olone, followed 2 days later by an important increase in pro-gesterone. Circulating levels of the steroids were barelydetectable and did not change in response to lesion. Theseresults demonstrate that the nervous system responds toinjurywith an increase in the local synthesis of pregnenolone,progesterone, and its 5a-reduced metabolites, consistentwith an important role of these neurosteroids in neuropro-tection and regeneration.

doi:10.1016/j.yfrne.2006.03.301

Abstracts / Frontiers in Neuroendocrinology 27 (2006) 111–117 117