Steroid transformations in pregnant mares: Metabolism of exogenous progestins and unusual metabolic activity in vivo and in vitro

Schutzer, William E.; Holtan, D. W.

doi:10.1016/0039-128x(95)00199-z

Cited by 22 publications

(33 citation statements)

References 9 publications

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“…These are difficult studies to conduct and steroid metabolism is complex, hence the results are not easy to interpret. Although affirming high levels of 5a-reductase and other metabolic activities in the placenta [49,50,92], it was also suggested that DHP might be synthesized from pregnenolone [94], without progesterone as an intermediate, if pregnenolone itself were a substrate for 5a-reductase [92,93]. Though intriguing, no convincing or direct evidence of this has yet emerged [194].…”

Section: The Luteo-placental Shiftmentioning

confidence: 98%

“…Because the allantochorionic placenta expresses high levels of 5a-reductase [41], the major site of DHP synthesis shifts from systemic conversion to reduction of progesterone by the placenta [49,50] before any escapes from the gravid uterus. Several studies have been conducted in pregnant [50,92,93] and nonpregnant [92] mares in vivo and using placental tissue in vitro [49] to elucidate pregnane metabolism that is specific to the placenta. These are difficult studies to conduct and steroid metabolism is complex, hence the results are not easy to interpret.…”

Section: The Luteo-placental Shiftmentioning

confidence: 99%

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Review of the reproductive endocrinology of the pregnant and parturient mare

Conley

2016

Theriogenology

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Section: The Luteo-placental Shiftmentioning

confidence: 98%

Section: The Luteo-placental Shiftmentioning

confidence: 99%

Review of the reproductive endocrinology of the pregnant and parturient mare

Conley

2016

Theriogenology

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“…Concentrations of 5α-DHP which are at least twenty times higher in the umbilical vein than artery are metabolised by the fetus into 3β5P and ββ-diol, probably in the liver, rather than the adrenals or gonads which do not possess the necessary enzymes (Chavatte et al 1997). 5α-DHP is also metabolised into 20α-5P and βα-diol, via 3β-5P, by the placenta and then excreted into the maternal circulation (Schutzer and Holtan 1996). Because P4 is metabolised within the placenta, little P4 is detected in the umbilical circulation (< 13 ng /ml) and virtually none in maternal plasma (< 0.5 ng/ml).…”

Section: Feto-placental Metabolism Of Progesteronementioning

confidence: 99%

“…However, the raised levels of 5α-DHP and other metabolites tend to refute this suggestion. An alternative metabolic pathway for 5α-DHP formation has been postulated via 3β-5P in the fetus (Schutzer and Holtan 1996; Figure 1) and, therefore, this may allow production of 5α-DHP and other metabolites even when there is placental compromise. Alternatively fetal P5 and progestagen production may be increased as a result of fetal stress and the lack of change in maternal P5 concentrations may simply reflect the rapid metabolism of P5 by the placenta.…”

Section: Gc-ms Analysismentioning

confidence: 99%

Plasma progestagens as markers of feto-placental health

Ousey¹,

Fowden²,

Rossdale³

et al. 2001

PHK

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SummaryThe pregnant mare produces many metabolites of progesterone (progestagens) which are present in high concentrations in maternal plasma in late gestation. Progesterone (P4) itself is undetectable during the second half of pregnancy. The role of these progestagens is not known but it is thought that they may regulate myometrial activity. The source of progestagens has been identified using mares which have had chronic catheters placed in fetal, umbilical and uterine blood vessels. The P4 precursor, pregnenolone (P5) is produced by the fetus and rapidly metabolised by the placenta/endometrium into P4 and other metabolites, notably 5α-pregnane-3,20-dione (5α-DHP). These metabolites reenter the fetal circulation and are then further metabolised by the fetus and placenta and excreted into the maternal circulation. Because the enzymes necessary to metabolise progestagens are present in both the fetus and placenta/endometrium, an intact and healthy feto-placental unit is necessary for their production and, presumably, for maintenance of myometrial quiescence. In healthy Thoroughbred (TB) and pony mares, total progestagen concentrations gradually increase during the last week(s) pre-partum and then decline 24 h before delivery. However, in mares which have placental damage and associated premature mammary development, total progestagen concentrations often are raised precociously and remain elevated until abortion or pre-term delivery. Many of their foals, although delivered before full term, demonstrate adrenocortical activity suggesting a relationship between adrenal development and maternal plasma progestagen concentrations. This relationship has been confirmed by studies in which fetuses or mares injected sequentially with adrenocorticotrophic hormone (ACTH), exhibit raised maternal progestagen concentrations. Because the fetus produces P5, possibly by the adrenal, metabolism of progestagens may be altered or enhanced if there is fetal stress and / or placental damage. In order to test this hypothesis, blood samples were collected from mares (7 TB, 1 pony) in late gestation (250-280 days) with clinical conditions such as placentitis, premature mammary development, vaginal discharge or colic. Specific progestagen profiles measured quantitatively using gas chromatography -mass spectrometry showed detectable levels of P4 and elevated metabolites (5α-DHP, ββ-diol, 20α-5P, βα-diol) compared with control mares at the same stage of pregnancy. Maternal P5 was not elevated. Progestagens were low in 2 mares which aborted within 72 h. These results suggest that the progestagen pathway may be blocked in the placenta whilst an alternative route for 5α-DHP production may exist in the fetus. Low maternal P5 concentrations do not preclude enhanced fetal P5 production, but low progestagen concentrations overall were associated with fetal demise. A specific marker of feto-placental stress was not identified but different progestagen profiles were observed between healthy and compromised pregnant mares. Keywords:progestagens, 5α...

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“…Não obstante, estudos in vitro demonstraram que o fígado fetal pode converter a P 5 em progestágenos (SCHUTZER; HOLTAN, 1996).…”

Section: Revisão De Literaturaunclassified

Avaliação hormonal sérica e estereológica da membrana corioalantóide a termo de éguas: influência no desenvolvimento e nos parâmetros clínicos e metabólicos do potro

Meirelles¹

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AgradecimentosÀ minha mãe (Carla) e minha vó (Carmen) que embora inicialmente não ficaram muito contentes com a ideia da minha mudança para São Paulo, sempre foram participativas e incentivaram os estudos e sei que estão muito orgulhosas por essa conquista. Obrigada por tudo! Este trabalho dedico a vocês... Ao meu irmão e melhor amigo, Hector, que sempre me achou a "nerd" da casa... Ao meu noivo e amigo Rafael... não existem palavras no dicionário que possam descrever o quanto sou grata por todo seu apoio e colaboração incondicional nesse projeto e na minha vida. Te amo para todo e sempre.Ao meu sogro, Roberto, e minha Sogra, Sandra, pelo apoio e carinho... À Faculdade de Medicina Veterinária e Zootecnia da Universidade de SãoPaulo, em especial o Departamento de Reprodução Animal, por proporcionar essa excelente oportunidade de aprimoramento científico, técnico, profissional e pessoal.À minha orientadora Prof. Dra. Claudia Barbosa Fernandes que me acolheu de braços abertos, aceitou esse grande desafio e sempre esteve presente e muito dedicada. Obrigada por acreditar em mim e vibrar por nossas conquistas. À minha colega de mestrado Carina Guimarães, obrigada pelo apoio na condução desse trabalho. Á Fazenda Santa Rita II e Centro de Reprodução TOK Genética, pela acolhida, empréstimo dos animais para o projeto, pelas inúmeras horas de plantões de madrugada e pelos potrinhos fofinhos para cuidar.Um agradecimento especial à Guta, que colaborou incansavelmente deste a elaboração, execução e finalização deste projeto. Muito obrigada por ser essa pessoa tão dedicada, participativa e incentivadora.Ao Dr. Eduardo Onoe, sempre muito prestativo. Obrigada por ter me acolhido em seu haras, dado todo apoio necessário, e confiado neste trabalho.Ao Zé, Fernanda, Kleber, Júlia, Andréia, Juliana, Danilo, Nara, Paloma, Muitos fatores podem influenciar o desenvolvimento placentário e fetal na égua, dentre eles destaca-se a idade, a paridade e o porte materno. A produção de hormônios esteroides pela unidade feto-placentária também pode ser influenciada pela paridade e raça, porém não existem relatos prévios que relacionem os efeitos da idade da égua sobre a produção desses hormônios na gestação. Este trabalho conta com três objetivos principais: o primeiro investigou a influência do número de partos e da idade materna sobre a eficiência placentária e a biometria do potro ao nascimento, utilizando a análise estereológica da placenta a termo. O segundo determinou a influencia da biometria parental na macro e microscopia placentária e consequências para o desenvolvimento fetal e para o crescimento, comportamento e funções fisiológicas pós-natais. Por último foi avaliada a influência da idade e paridade materna, e da raça do potro sob a produção de estrógenos, progesterona e cortisol plasmáticos em éguas prenhes. Quarenta fêmeas gestantes foram Many factors may influence placental and fetal development in the mare, like age, parity and maternal size. The production of steroid hormones by fetal-placental unit can also be influenced by pa...

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Steroid transformations in pregnant mares: Metabolism of exogenous progestins and unusual metabolic activity in vivo and in vitro

Cited by 22 publications

References 9 publications

Review of the reproductive endocrinology of the pregnant and parturient mare

Review of the reproductive endocrinology of the pregnant and parturient mare

Plasma progestagens as markers of feto-placental health

Avaliação hormonal sérica e estereológica da membrana corioalantóide a termo de éguas: influência no desenvolvimento e nos parâmetros clínicos e metabólicos do potro

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