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341. Hippocampal function and corticosterone receptors: implication in behavioral processes
882
Abslracts
3.1 x IO “’ M). Tc\tosicronc (IO ’ M) and corticosterone (Ill ” M) had no CITCCIon tither E-induced PRL symhesis l)r k,n cstrogcn rcccpcor Ie\cls. Our dara suggest that P lnhihlts E-tnduced PRL synthchis by decreasing the numhcr 01’ cstrogcn rcccptor silts and thereby reducing I~C numhcr of E-rcccptor complcxch that are translocated to the <;H,, cell nuclei.
3.W. Patterns of corticotrophin releasing factor (CRF) production from the rat hypothalamus isolated and incubated in vitro K~MSIWA. G.. TII~WAS. P. and SALWW. J. I. D.. Departmcnt ol’ Physiology. Medical Sclcncch. University ol’ Lclccstcr. U.K. Although I he WI/W/ 01 corticotrophm rclca,ing ractor (CRF) has bcsn round IO vary with the 14 h cycle. producIIOI~ and rclcasc h;t\c not been estimated. Output or CRF U;I~ mcasurcd III various tlmcs over the 24 h period by means ol a trlplc ,,I rirrr~ bioassay. the resultant cortico\tcronc being mcasurcd tluorimetrically. Results l’rom both incubaticjn.\ showed that production of CRF from the r31 hypolh;llamus \arles o\cr the 14 h cycle. In the first ~ncub;ltion. ~hc rclall\e potency Increases 3-fold IO a peak at IXtW) h ml111;I prcccding trough during the day. The second I min Incubation showed ;I similar variation with a phasead\ancc or 2 h. i.c. :I peak ai 1600 h. Results from incubaIIC~II 2 parallel the plasma cortlcosterone levels more closely 1han results l’rom incubation I. However. Incubat~on I productton gave similar values to those obtained hy other workers cytlmating W~I!W~ of hypothalamic CRF. II IX thcrcl’orc tentatively concluded from these resubs that thcrc may he more than one pool of CRF abailable in the hypo1halamus: ;II IWSI that of a “content”. and that of W&I! sqnthcslzcd CRF.
339. Relative importance of corticosteroid negative feedback at the adenohypophysis and the hypothalamus GII.I.IIAM. B..* M~WOUD. S. and JONES. M. T.. Departments ol’ Physiology and *Biochemistry. St. Thomas’s Hospital Medical School. London. U.K. T\ro types or negat~vc lecdback arc demonstrable III the corticosteroid administration. rat 111 rirc~. folloHlng fast-(FFB) and delayed-(DFB) feedback. Both aspects of feedback are demonstrable separately at the adenohypophysts (AH) and at the hypothalamus (HP). FFB in rirm occurs a~ the HP with lower doses of corticosterone (B) than at the AH. DOC and I I-deoxycortisol are antagonists of FFB both in intac1 animals and at the HP iu vitro. but are agonists when tested on the AH. Similar findings apply to DFB. Progesterone and l72-OH pregnenolone are without effect either 31 the HP or in intact animals. but both are agonists of DFB a1 the AH. These two srcroids. therefore.can exert a DFB etTect a~ 1he AH under circumstances where they have little influence on ACTH secretion in ~mact animals. These data suggest that DFB and FFB ;~1 the HP are physiologically more important than at the AH.
340. Effect of testosterow and of its h-reduced metabolites on the secretion of LH and FSH J~NEJA. H. S.. MOTTA. M. and MARTINI. L.. lstituto di Endocrinologla. Via Andrea de1 Sarto-21. Milan. Italy A longitudtnal study of the effects of median eminence (ME) implants of testosterone (T). Sz-androslan-I 78-ol-3one (DHT). 5x-androstane-3a. 17/?diol (3zdiol) and 5x-androstane-3/?-I 7/?-diol (3fidiol) on rhe serum levels of
LH and FSH has been perl’ormed in adult caslrared male rats. Blood was collected before and I. 3. 5. 7 and 9 days alier ME. Sham operations did not affect serum levels of tither gonadotropins. T. DHT and 3z-dial reduced the levels or LH: 3p-dial was inemectire. The elTec1 of T -as transient while that of DHT and of 3adiol was more prolonged. T and DHT Increased the serum levels of FSH above control values at all post-implantation times studied. These studies suggest a modulatory role of T and its 5x-reduced metabolites on the secretion of gonadolropins both at the hypothalamic and at the pituitary lebels. In particular. rhey suggest that (I I T may operate on the Feedback mechanism controlling LH secretion after IIS reduc1mn In the 5n-position: (2) T and DHT might exert a “pos~t~vc” feed-back etTect on FSH release.
341. Hippocampal function and corticosterone plication in behavioral processes &)HUS. B.. NYAKAS. C. and DE KLWT. Magnus Institute for Pharmacology. Utrecht. Utrecht. The Netherlands
receptors: imE. R.. Rudolf University of
The hippocampus plays an important role In the regulation of adaptive behavior. Corticosteroids appear to modulate behavioral processes. The presence of corticosterone receptors in rat hlppocampus suggests that a receptor-corticosterone (B) interaction may be the cellular basis of the behavioral modulation. The significance of hippocampal B receptors was mvestlgated via IUO essentially dimerem approaches. First. impaired extinction behavior is observed I h after adrenalectomy: this dekit can be corrected h? substitution of a small amount of B. The potent synthetic glucocorticoid dexamethasone IS actnc only in a 25 llrnes higher dose. Dexamethasone or progesterone even attenuate the effect of B. probably through competition for specific hlppocampal B receptor sues. The observations favour the involvement of specific B receptors in behavIoral regulation. Second. des1ruction of the medial septal nuclei abolishes hippocampal thera acr~v~ty but does not atTect the activity of B receptors in the hippocampus. Lateral and postero-lateral septal lesions including the preand postcommisural rornix increase the activity of B receptors and result in an lmpalrment in avoidance behavior. Control experiments wi1h lesions in the posterior thalamus indicate that changes in receptor act~vlty are not due IO the behavioral Impairment. It seems that the activity of B receptors depends upon the integrity of the efferentation or the hippocampus and or of rhe lateral sepfal B receptors
342. Neuruendocrine relatiomhips in mammalian uterus THORBERT. G.. ALM. P.. BATRA. S.. OW~AN. CH. and SJ~~BERG.N.-O.. Departments of Obstetrics & Gynecology and Histology. Unirerslty of Lund. Sweden The amount of sympathetic neurotransmitters. noradrenaline (NAI can be experimentally changed in the uterus by various sex steroid treatments (in rabbits) or by ovariectomy (in guinea-pigs). In order to relate such transmitter changes (reflecting neuronal events) 10 sex hormone levels. rabbi1 pseudopregnancy was studied by measurements of tissue NA (Ruorimetricallyl as well as plasma and tissue concentration or progesterone (P) and estradiol-17/3 (E,: radioimmunoassays). Uterine wet weight increased considerably. simultaneously with a decay in the NA content (,cp per uterus). In parallel with this. tissue P concentration increased 4-lold and tissue Ez concentration decreased to about one fifth. Maximum tissue P concentration and minimum tissue EI level were observed on the 6th day. when the NA content was lowest and weight gain was maximal. On days 12 and 18 a nearly full restitution to
Abslracts
3.1 x IO “’ M). Tc\tosicronc (IO ’ M) and corticosterone (Ill ” M) had no CITCCIon tither E-induced PRL symhesis l)r k,n cstrogcn rcccpcor Ie\cls. Our dara suggest that P lnhihlts E-tnduced PRL synthchis by decreasing the numhcr 01’ cstrogcn rcccptor silts and thereby reducing I~C numhcr of E-rcccptor complcxch that are translocated to the <;H,, cell nuclei.
3.W. Patterns of corticotrophin releasing factor (CRF) production from the rat hypothalamus isolated and incubated in vitro K~MSIWA. G.. TII~WAS. P. and SALWW. J. I. D.. Departmcnt ol’ Physiology. Medical Sclcncch. University ol’ Lclccstcr. U.K. Although I he WI/W/ 01 corticotrophm rclca,ing ractor (CRF) has bcsn round IO vary with the 14 h cycle. producIIOI~ and rclcasc h;t\c not been estimated. Output or CRF U;I~ mcasurcd III various tlmcs over the 24 h period by means ol a trlplc ,,I rirrr~ bioassay. the resultant cortico\tcronc being mcasurcd tluorimetrically. Results l’rom both incubaticjn.\ showed that production of CRF from the r31 hypolh;llamus \arles o\cr the 14 h cycle. In the first ~ncub;ltion. ~hc rclall\e potency Increases 3-fold IO a peak at IXtW) h ml111;I prcccding trough during the day. The second I min Incubation showed ;I similar variation with a phasead\ancc or 2 h. i.c. :I peak ai 1600 h. Results from incubaIIC~II 2 parallel the plasma cortlcosterone levels more closely 1han results l’rom incubation I. However. Incubat~on I productton gave similar values to those obtained hy other workers cytlmating W~I!W~ of hypothalamic CRF. II IX thcrcl’orc tentatively concluded from these resubs that thcrc may he more than one pool of CRF abailable in the hypo1halamus: ;II IWSI that of a “content”. and that of W&I! sqnthcslzcd CRF.
339. Relative importance of corticosteroid negative feedback at the adenohypophysis and the hypothalamus GII.I.IIAM. B..* M~WOUD. S. and JONES. M. T.. Departments ol’ Physiology and *Biochemistry. St. Thomas’s Hospital Medical School. London. U.K. T\ro types or negat~vc lecdback arc demonstrable III the corticosteroid administration. rat 111 rirc~. folloHlng fast-(FFB) and delayed-(DFB) feedback. Both aspects of feedback are demonstrable separately at the adenohypophysts (AH) and at the hypothalamus (HP). FFB in rirm occurs a~ the HP with lower doses of corticosterone (B) than at the AH. DOC and I I-deoxycortisol are antagonists of FFB both in intac1 animals and at the HP iu vitro. but are agonists when tested on the AH. Similar findings apply to DFB. Progesterone and l72-OH pregnenolone are without effect either 31 the HP or in intact animals. but both are agonists of DFB a1 the AH. These two srcroids. therefore.can exert a DFB etTect a~ 1he AH under circumstances where they have little influence on ACTH secretion in ~mact animals. These data suggest that DFB and FFB ;~1 the HP are physiologically more important than at the AH.
340. Effect of testosterow and of its h-reduced metabolites on the secretion of LH and FSH J~NEJA. H. S.. MOTTA. M. and MARTINI. L.. lstituto di Endocrinologla. Via Andrea de1 Sarto-21. Milan. Italy A longitudtnal study of the effects of median eminence (ME) implants of testosterone (T). Sz-androslan-I 78-ol-3one (DHT). 5x-androstane-3a. 17/?diol (3zdiol) and 5x-androstane-3/?-I 7/?-diol (3fidiol) on rhe serum levels of
LH and FSH has been perl’ormed in adult caslrared male rats. Blood was collected before and I. 3. 5. 7 and 9 days alier ME. Sham operations did not affect serum levels of tither gonadotropins. T. DHT and 3z-dial reduced the levels or LH: 3p-dial was inemectire. The elTec1 of T -as transient while that of DHT and of 3adiol was more prolonged. T and DHT Increased the serum levels of FSH above control values at all post-implantation times studied. These studies suggest a modulatory role of T and its 5x-reduced metabolites on the secretion of gonadolropins both at the hypothalamic and at the pituitary lebels. In particular. rhey suggest that (I I T may operate on the Feedback mechanism controlling LH secretion after IIS reduc1mn In the 5n-position: (2) T and DHT might exert a “pos~t~vc” feed-back etTect on FSH release.
341. Hippocampal function and corticosterone plication in behavioral processes &)HUS. B.. NYAKAS. C. and DE KLWT. Magnus Institute for Pharmacology. Utrecht. Utrecht. The Netherlands
receptors: imE. R.. Rudolf University of
The hippocampus plays an important role In the regulation of adaptive behavior. Corticosteroids appear to modulate behavioral processes. The presence of corticosterone receptors in rat hlppocampus suggests that a receptor-corticosterone (B) interaction may be the cellular basis of the behavioral modulation. The significance of hippocampal B receptors was mvestlgated via IUO essentially dimerem approaches. First. impaired extinction behavior is observed I h after adrenalectomy: this dekit can be corrected h? substitution of a small amount of B. The potent synthetic glucocorticoid dexamethasone IS actnc only in a 25 llrnes higher dose. Dexamethasone or progesterone even attenuate the effect of B. probably through competition for specific hlppocampal B receptor sues. The observations favour the involvement of specific B receptors in behavIoral regulation. Second. des1ruction of the medial septal nuclei abolishes hippocampal thera acr~v~ty but does not atTect the activity of B receptors in the hippocampus. Lateral and postero-lateral septal lesions including the preand postcommisural rornix increase the activity of B receptors and result in an lmpalrment in avoidance behavior. Control experiments wi1h lesions in the posterior thalamus indicate that changes in receptor act~vlty are not due IO the behavioral Impairment. It seems that the activity of B receptors depends upon the integrity of the efferentation or the hippocampus and or of rhe lateral sepfal B receptors
342. Neuruendocrine relatiomhips in mammalian uterus THORBERT. G.. ALM. P.. BATRA. S.. OW~AN. CH. and SJ~~BERG.N.-O.. Departments of Obstetrics & Gynecology and Histology. Unirerslty of Lund. Sweden The amount of sympathetic neurotransmitters. noradrenaline (NAI can be experimentally changed in the uterus by various sex steroid treatments (in rabbits) or by ovariectomy (in guinea-pigs). In order to relate such transmitter changes (reflecting neuronal events) 10 sex hormone levels. rabbi1 pseudopregnancy was studied by measurements of tissue NA (Ruorimetricallyl as well as plasma and tissue concentration or progesterone (P) and estradiol-17/3 (E,: radioimmunoassays). Uterine wet weight increased considerably. simultaneously with a decay in the NA content (,cp per uterus). In parallel with this. tissue P concentration increased 4-lold and tissue Ez concentration decreased to about one fifth. Maximum tissue P concentration and minimum tissue EI level were observed on the 6th day. when the NA content was lowest and weight gain was maximal. On days 12 and 18 a nearly full restitution to