Longitudinal serum and urine steroid metabolite profiling in a 46,XY infant with prenatally identified POR deficiency
Longitudinal serum and urine steroid metabolite profiling in a 46,XY infant with prenatally identified POR deficiency
复制标题
产前发现 POR 缺陷的 46,XY 婴儿的纵向血清和尿液类固醇代谢物分析
DOI：
10.1016/j.jsbmb.2017.12.008
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Ogata Tsutomu
中科院分区：
文献类型：
--
作者：
Ono Hiroyuki;Numakura Chikahiko;Homma Keiko;Hasegawa Tomonobu;Tsutsumi Seiji;Kato Fumiko;Fujisawa Yasuko;Fukami Maki;Ogata Tsutomu
虽然POR缺乏症(PORD)被认为伴随着胎盘雄激素过多积聚，肾上腺和睾丸雄激素分泌通过后门途径增加，以及睾丸雄激素分泌通过前门途径受损，但没有直接证据表明过多的胎盘雄激素流入胎儿血液循环，并通过后门途径产生双氢睾酮(DHT)。我们检测了一例46，XY PORD婴儿的血清和尿中类固醇代谢产物的纵向谱，该婴儿出生前被鉴定为POR(p.Q201X和p.R457H)复合杂合突变，其原因是孕中期胎儿逐渐男性化和母体男性化。结果显示：(1)出生时血清雄烯二酮和睾酮(T)值显著和不适当地升高，(2)出生时血清DHT值显著升高，dht/T比值正常，(3)出生时血清T和DHT值一过性升高，并伴随着30 日龄时前门和后门通路中间类固醇代谢物的升高，(4)持续的PORD相容的尿类固醇谱。虽然从单个婴儿患者身上获得的数据还为时过早，不能一概而论，但它们暗示：(1)从妊娠中期开始，过量的胎盘雄激素转移到胎儿和母亲的血液循环中，(2)在出生前后缺乏临床上可识别的通过肾上腺后门途径产生的DHT，以及(3)在小青春期前后睾丸的前门和后门途径都被激活，没有通过睾丸后门途径产生临床可识别的DHT。
Although POR deficiency (PORD) is assumed to be accompanied by excessive placental androgen accumulation and enhanced adrenal and testicular androgen production via the backdoor pathway as well as compromised testicular androgen production via the frontdoor pathway, there is no direct evidence for the flux of excessive placental androgens into the fetal circulation and for the production of dihydrotestosterone (DHT) via the backdoor pathway. We examined longitudinal serum and urine steroid metabolite profiles in a 46,XY infant with PORD who was prenatally identified because of the progressive fetal masculinization and maternal virilization from the mid-gestation and the presence of fetal radio-humeral synostosis and was confirmed to have compound heterozygous mutations ofPOR(p.Q201X and p.R457H). The results showed (1) markedly and inappropriately elevated serum androstenedione and testosterone (T) values at birth, (2) a markedly increased serum DHT value with a normal DHT/T ratio at birth, (3) transient elevation of serum T and DHT values accompanied by a normal DHT/T ratio and concomitant elevations of intermediate steroid metabolites on both the frontdoor and backdoor pathways at 30 days of age, and (4) persistent PORD-compatible urine steroid profiles. Although the data obtained from a single infantile patient are too premature to be generalized, they imply: (1) the transfer of excessive placental androgens into the fetal as well as the maternal circulations from the mid-gestation, (2) lack of a clinically discernible amount of DHT production via the adrenal backdoor pathway around birth, and (3) the activation of both the frontdoor and backdoor pathways in the testis around the mini-puberty, with no production of a clinically discernible amount of DHT via the testicular backdoor pathway.
登录
查看更多内容
影响因子：
5.8
作者：
Kamrath, Clemens;Hochberg, Ze'ev;Wudy, Stefan A.
通讯作者：
Wudy, Stefan A.
第 21 章 – 妊娠期内分泌变化
DOI：
--
发表时间：
2011
期刊：
影响因子：
--
作者：
G. Braunstein
通讯作者：
G. Braunstein
影响因子：
2.9
作者：
Savchuk I;Morvan ML;Antignac JP;Gemzell-Danielsson K;Le Bizec B;Söder O;Svechnikov K
通讯作者：
Svechnikov K
雌激素：人类合成和作用突变的后果和影响。
DOI：
10.1210/jcem.84.12.6290
发表时间：
1999
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Grumbach,MM;Auchus,RJ
通讯作者：
Auchus,RJ
DOI：
10.1016/j.jsbmb.2016.07.009
发表时间：
2017-01-01
影响因子：
4.1
作者：
Dhayat, Nasser A.;Dick, Bernhard;Fluck, Christa E.
通讯作者：
Fluck, Christa E.