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Cortisol, aldosterone, cortisol precursor, androgen and endogenous ACTH concentrations in dogs with pituitary-dependant hyperadrenocorticism treated with trilostane
Trilostane is thought to be a competitive inhibitor of the 3β-hydroxysteroid dehydrogenase (3β-HSD), an essential enzyme system for the synthesis of cortisol, aldosterone and androstenedione. Due to its reliable clinical efficacy, trilostane is increasingly used to treat dogs with pituitary-dependan...
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| Published in: | Domestic animal endocrinology 2006-07, Vol.31 (1), p.63-75 |
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| creator | Sieber-Ruckstuhl, N.S. Boretti, F.S. Wenger, M. Maser-Gluth, C. Reusch, C.E. |
| description | Trilostane is thought to be a competitive inhibitor of the 3β-hydroxysteroid dehydrogenase (3β-HSD), an essential enzyme system for the synthesis of cortisol, aldosterone and androstenedione. Due to its reliable clinical efficacy, trilostane is increasingly used to treat dogs with pituitary-dependant hyperadrenocorticism (PDH).
The objective of our study was to investigate the effect of trilostane on precursor concentrations located before (17α-OH-pregnenolone, dehydroepiandrostenedione) and after (17α-OH-progesterone, androstenedione, 11-deoxycortisol, 21-deoxycortisol) the proposed enzyme inhibition, on end products of steroid biosynthesis (cortisol and aldosterone) and on endogenous adrenocorticotrophic hormone (ACTH) concentrations in dogs with PDH. Hormones of the steroid biosynthesis pathway were evaluated in 15 dogs before and 1
h after injection of synthetic ACTH prior to (
t
0), in weeks 1–2 (
t
1) and in weeks 3–7 (
t
2) of trilostane treatment. Endogenous ACTH concentrations were measured at the same time points before performing the ACTH stimulation test.
During trilostane treatment baseline and post-stimulation cortisol concentrations decreased significantly. Baseline serum aldosterone levels showed a significant increase; post-stimulation values decreased. Baseline and post-stimulation 17α-OH-pregnenolone and dehydroepiandrostenedione concentrations increased significantly. 17α-OH-progesterone and androstenedione levels did not change. Post-stimulation 21-deoxycortisol concentrations decreased significantly, baseline 11-deoxycortisol concentrations increased significantly. Endogenous ACTH levels showed a significant increase.
The significant increase in 17α-OH-pregnenolone and dehydroepiandrostenedione concentrations confirms an inhibitory effect of trilostane on the 3β-HSD. Since 17α-OH-progesterone concentrations did not change, but cortisol concentrations markedly decreased, trilostane seems to influence additional enzymes of the hormone cascade, like the 11β-hydroxylase and possibly the 11β-hydroxysteroid dehydrogenase. |
| doi_str_mv | 10.1016/j.domaniend.2005.09.004 |
| format | article |
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The objective of our study was to investigate the effect of trilostane on precursor concentrations located before (17α-OH-pregnenolone, dehydroepiandrostenedione) and after (17α-OH-progesterone, androstenedione, 11-deoxycortisol, 21-deoxycortisol) the proposed enzyme inhibition, on end products of steroid biosynthesis (cortisol and aldosterone) and on endogenous adrenocorticotrophic hormone (ACTH) concentrations in dogs with PDH. Hormones of the steroid biosynthesis pathway were evaluated in 15 dogs before and 1
h after injection of synthetic ACTH prior to (
t
0), in weeks 1–2 (
t
1) and in weeks 3–7 (
t
2) of trilostane treatment. Endogenous ACTH concentrations were measured at the same time points before performing the ACTH stimulation test.
During trilostane treatment baseline and post-stimulation cortisol concentrations decreased significantly. Baseline serum aldosterone levels showed a significant increase; post-stimulation values decreased. Baseline and post-stimulation 17α-OH-pregnenolone and dehydroepiandrostenedione concentrations increased significantly. 17α-OH-progesterone and androstenedione levels did not change. Post-stimulation 21-deoxycortisol concentrations decreased significantly, baseline 11-deoxycortisol concentrations increased significantly. Endogenous ACTH levels showed a significant increase.
The significant increase in 17α-OH-pregnenolone and dehydroepiandrostenedione concentrations confirms an inhibitory effect of trilostane on the 3β-HSD. Since 17α-OH-progesterone concentrations did not change, but cortisol concentrations markedly decreased, trilostane seems to influence additional enzymes of the hormone cascade, like the 11β-hydroxylase and possibly the 11β-hydroxysteroid dehydrogenase.</description><identifier>ISSN: 0739-7240</identifier><identifier>EISSN: 1879-0054</identifier><identifier>DOI: 10.1016/j.domaniend.2005.09.004</identifier><identifier>PMID: 16233969</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>17-alpha-Hydroxypregnenolone - blood ; 3-Hydroxysteroid Dehydrogenases - antagonists & inhibitors ; Adrenocortical Hyperfunction - blood ; Adrenocortical Hyperfunction - drug therapy ; Adrenocortical Hyperfunction - veterinary ; Adrenocorticotropic Hormone - blood ; Aldosterone - blood ; Androstenedione - blood ; Animals ; Cortodoxone - blood ; Dehydroepiandrosterone - blood ; Dihydrotestosterone - analogs & derivatives ; Dihydrotestosterone - therapeutic use ; Dog Diseases - blood ; Dog Diseases - drug therapy ; Dogs ; Endogenous ACTH ; Enzyme Inhibitors - therapeutic use ; Female ; Hydrocortisone - blood ; Hyperadrenocorticism ; Male ; Prospective Studies ; Statistics, Nonparametric ; Steroid hormone concentrations ; Trilostane</subject><ispartof>Domestic animal endocrinology, 2006-07, Vol.31 (1), p.63-75</ispartof><rights>2005 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c369t-a349d22f675984e0c0024dad492eb82d8d13c4dee9d5b5a4b76acc73d5429f8f3</citedby><cites>FETCH-LOGICAL-c369t-a349d22f675984e0c0024dad492eb82d8d13c4dee9d5b5a4b76acc73d5429f8f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16233969$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sieber-Ruckstuhl, N.S.</creatorcontrib><creatorcontrib>Boretti, F.S.</creatorcontrib><creatorcontrib>Wenger, M.</creatorcontrib><creatorcontrib>Maser-Gluth, C.</creatorcontrib><creatorcontrib>Reusch, C.E.</creatorcontrib><title>Cortisol, aldosterone, cortisol precursor, androgen and endogenous ACTH concentrations in dogs with pituitary-dependant hyperadrenocorticism treated with trilostane</title><title>Domestic animal endocrinology</title><addtitle>Domest Anim Endocrinol</addtitle><description>Trilostane is thought to be a competitive inhibitor of the 3β-hydroxysteroid dehydrogenase (3β-HSD), an essential enzyme system for the synthesis of cortisol, aldosterone and androstenedione. Due to its reliable clinical efficacy, trilostane is increasingly used to treat dogs with pituitary-dependant hyperadrenocorticism (PDH).
The objective of our study was to investigate the effect of trilostane on precursor concentrations located before (17α-OH-pregnenolone, dehydroepiandrostenedione) and after (17α-OH-progesterone, androstenedione, 11-deoxycortisol, 21-deoxycortisol) the proposed enzyme inhibition, on end products of steroid biosynthesis (cortisol and aldosterone) and on endogenous adrenocorticotrophic hormone (ACTH) concentrations in dogs with PDH. Hormones of the steroid biosynthesis pathway were evaluated in 15 dogs before and 1
h after injection of synthetic ACTH prior to (
t
0), in weeks 1–2 (
t
1) and in weeks 3–7 (
t
2) of trilostane treatment. Endogenous ACTH concentrations were measured at the same time points before performing the ACTH stimulation test.
During trilostane treatment baseline and post-stimulation cortisol concentrations decreased significantly. Baseline serum aldosterone levels showed a significant increase; post-stimulation values decreased. Baseline and post-stimulation 17α-OH-pregnenolone and dehydroepiandrostenedione concentrations increased significantly. 17α-OH-progesterone and androstenedione levels did not change. Post-stimulation 21-deoxycortisol concentrations decreased significantly, baseline 11-deoxycortisol concentrations increased significantly. Endogenous ACTH levels showed a significant increase.
The significant increase in 17α-OH-pregnenolone and dehydroepiandrostenedione concentrations confirms an inhibitory effect of trilostane on the 3β-HSD. Since 17α-OH-progesterone concentrations did not change, but cortisol concentrations markedly decreased, trilostane seems to influence additional enzymes of the hormone cascade, like the 11β-hydroxylase and possibly the 11β-hydroxysteroid dehydrogenase.</description><subject>17-alpha-Hydroxypregnenolone - blood</subject><subject>3-Hydroxysteroid Dehydrogenases - antagonists & inhibitors</subject><subject>Adrenocortical Hyperfunction - blood</subject><subject>Adrenocortical Hyperfunction - drug therapy</subject><subject>Adrenocortical Hyperfunction - veterinary</subject><subject>Adrenocorticotropic Hormone - blood</subject><subject>Aldosterone - blood</subject><subject>Androstenedione - blood</subject><subject>Animals</subject><subject>Cortodoxone - blood</subject><subject>Dehydroepiandrosterone - blood</subject><subject>Dihydrotestosterone - analogs & derivatives</subject><subject>Dihydrotestosterone - therapeutic use</subject><subject>Dog Diseases - blood</subject><subject>Dog Diseases - drug therapy</subject><subject>Dogs</subject><subject>Endogenous ACTH</subject><subject>Enzyme Inhibitors - therapeutic use</subject><subject>Female</subject><subject>Hydrocortisone - blood</subject><subject>Hyperadrenocorticism</subject><subject>Male</subject><subject>Prospective Studies</subject><subject>Statistics, Nonparametric</subject><subject>Steroid hormone concentrations</subject><subject>Trilostane</subject><issn>0739-7240</issn><issn>1879-0054</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNqFUU2P0zAQtRCILQt_AXzitAkTx_nwsaoWFmklLsvZcu0J6yqxg-2C9v_wQ5nSCo6cPBq_j3l6jL1roG6g6T8cahcXEzwGVwuArgZVA8hnbNOMg6poI5-zDQytqgYh4Yq9yvkAAAOxX7Krphdtq3q1Yb92MRWf43zDzexiLphiwBtuL2u-JrTHlGMiQHApfsNwGjg5n-Z4zHy7e7gjQrAYSjLFx5C5D5z-M__pyyNffTn6YtJT5XAlogmFPz6tmIxLJPHHy_q88JLQFHRnVkl-poNMwNfsxWTmjG8u7zX7-vH2YXdX3X_59Hm3va9s26tSmVYqJ8TUD50aJYIFENIZJ5XA_Sjc6JrWSoeoXLfvjNwPvbF2aF0nhZrGqb1m78-6a4rfj5iLXny2OM90AwXV_QhiBAUEHM5Am2LOCSe9Jr9QQN2APhWkD_pvQfpUkAalqSBivr1YHPcLun-8SyME2J4BSEF_eEw6W1Kx6Dw1UUjW_9fkN6oNrBw</recordid><startdate>20060701</startdate><enddate>20060701</enddate><creator>Sieber-Ruckstuhl, N.S.</creator><creator>Boretti, F.S.</creator><creator>Wenger, M.</creator><creator>Maser-Gluth, C.</creator><creator>Reusch, C.E.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20060701</creationdate><title>Cortisol, aldosterone, cortisol precursor, androgen and endogenous ACTH concentrations in dogs with pituitary-dependant hyperadrenocorticism treated with trilostane</title><author>Sieber-Ruckstuhl, N.S. ; Boretti, F.S. ; Wenger, M. ; Maser-Gluth, C. ; Reusch, C.E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c369t-a349d22f675984e0c0024dad492eb82d8d13c4dee9d5b5a4b76acc73d5429f8f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>17-alpha-Hydroxypregnenolone - blood</topic><topic>3-Hydroxysteroid Dehydrogenases - antagonists & inhibitors</topic><topic>Adrenocortical Hyperfunction - blood</topic><topic>Adrenocortical Hyperfunction - drug therapy</topic><topic>Adrenocortical Hyperfunction - veterinary</topic><topic>Adrenocorticotropic Hormone - blood</topic><topic>Aldosterone - blood</topic><topic>Androstenedione - blood</topic><topic>Animals</topic><topic>Cortodoxone - blood</topic><topic>Dehydroepiandrosterone - blood</topic><topic>Dihydrotestosterone - analogs & derivatives</topic><topic>Dihydrotestosterone - therapeutic use</topic><topic>Dog Diseases - blood</topic><topic>Dog Diseases - drug therapy</topic><topic>Dogs</topic><topic>Endogenous ACTH</topic><topic>Enzyme Inhibitors - therapeutic use</topic><topic>Female</topic><topic>Hydrocortisone - blood</topic><topic>Hyperadrenocorticism</topic><topic>Male</topic><topic>Prospective Studies</topic><topic>Statistics, Nonparametric</topic><topic>Steroid hormone concentrations</topic><topic>Trilostane</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sieber-Ruckstuhl, N.S.</creatorcontrib><creatorcontrib>Boretti, F.S.</creatorcontrib><creatorcontrib>Wenger, M.</creatorcontrib><creatorcontrib>Maser-Gluth, C.</creatorcontrib><creatorcontrib>Reusch, C.E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Domestic animal endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sieber-Ruckstuhl, N.S.</au><au>Boretti, F.S.</au><au>Wenger, M.</au><au>Maser-Gluth, C.</au><au>Reusch, C.E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cortisol, aldosterone, cortisol precursor, androgen and endogenous ACTH concentrations in dogs with pituitary-dependant hyperadrenocorticism treated with trilostane</atitle><jtitle>Domestic animal endocrinology</jtitle><addtitle>Domest Anim Endocrinol</addtitle><date>2006-07-01</date><risdate>2006</risdate><volume>31</volume><issue>1</issue><spage>63</spage><epage>75</epage><pages>63-75</pages><issn>0739-7240</issn><eissn>1879-0054</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Trilostane is thought to be a competitive inhibitor of the 3β-hydroxysteroid dehydrogenase (3β-HSD), an essential enzyme system for the synthesis of cortisol, aldosterone and androstenedione. Due to its reliable clinical efficacy, trilostane is increasingly used to treat dogs with pituitary-dependant hyperadrenocorticism (PDH).
The objective of our study was to investigate the effect of trilostane on precursor concentrations located before (17α-OH-pregnenolone, dehydroepiandrostenedione) and after (17α-OH-progesterone, androstenedione, 11-deoxycortisol, 21-deoxycortisol) the proposed enzyme inhibition, on end products of steroid biosynthesis (cortisol and aldosterone) and on endogenous adrenocorticotrophic hormone (ACTH) concentrations in dogs with PDH. Hormones of the steroid biosynthesis pathway were evaluated in 15 dogs before and 1
h after injection of synthetic ACTH prior to (
t
0), in weeks 1–2 (
t
1) and in weeks 3–7 (
t
2) of trilostane treatment. Endogenous ACTH concentrations were measured at the same time points before performing the ACTH stimulation test.
During trilostane treatment baseline and post-stimulation cortisol concentrations decreased significantly. Baseline serum aldosterone levels showed a significant increase; post-stimulation values decreased. Baseline and post-stimulation 17α-OH-pregnenolone and dehydroepiandrostenedione concentrations increased significantly. 17α-OH-progesterone and androstenedione levels did not change. Post-stimulation 21-deoxycortisol concentrations decreased significantly, baseline 11-deoxycortisol concentrations increased significantly. Endogenous ACTH levels showed a significant increase.
The significant increase in 17α-OH-pregnenolone and dehydroepiandrostenedione concentrations confirms an inhibitory effect of trilostane on the 3β-HSD. Since 17α-OH-progesterone concentrations did not change, but cortisol concentrations markedly decreased, trilostane seems to influence additional enzymes of the hormone cascade, like the 11β-hydroxylase and possibly the 11β-hydroxysteroid dehydrogenase.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>16233969</pmid><doi>10.1016/j.domaniend.2005.09.004</doi><tpages>13</tpages></addata></record> |
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| ispartof | Domestic animal endocrinology, 2006-07, Vol.31 (1), p.63-75 |
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| source | ScienceDirect Freedom Collection |
| subjects | 17-alpha-Hydroxypregnenolone - blood 3-Hydroxysteroid Dehydrogenases - antagonists & inhibitors Adrenocortical Hyperfunction - blood Adrenocortical Hyperfunction - drug therapy Adrenocortical Hyperfunction - veterinary Adrenocorticotropic Hormone - blood Aldosterone - blood Androstenedione - blood Animals Cortodoxone - blood Dehydroepiandrosterone - blood Dihydrotestosterone - analogs & derivatives Dihydrotestosterone - therapeutic use Dog Diseases - blood Dog Diseases - drug therapy Dogs Endogenous ACTH Enzyme Inhibitors - therapeutic use Female Hydrocortisone - blood Hyperadrenocorticism Male Prospective Studies Statistics, Nonparametric Steroid hormone concentrations Trilostane |
| title | Cortisol, aldosterone, cortisol precursor, androgen and endogenous ACTH concentrations in dogs with pituitary-dependant hyperadrenocorticism treated with trilostane |
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