Dose-dependent effects of arginine vasopressin on endocrine and blood gas responses of fetal sheep during the last third of pregnancy

We examined the hypothesis that estradiol (E2) would affect fetal anterior pituitary corticotroph and lactotroph function in vitro, and that any effects would be influenced by gestational age. Anterior pituitary cells from fetal sheep at day 129 (n = 4) and at day 139 (n = 5) of gestation were cultured. After 96 h in culture, cells were treated for 18 h with E2 concentrations ranging from 0 to 1000 nM, in the presence or absence of 100 nM of corticotropin-releasing hormone (CRH), cortisol, arginine vasopressin (AVP), or CRH and cortisol, to examine their effects on corticotroph function. Cells were also treated with bromocriptine or increasing concentrations of E2 to study their effects on lactotroph function. Immunoreactive (ir) adrenocorticotropin (ACTH) and prolactin in the culture medium were measured by radioimmunoassay. Levels of cellular pro-opiomelanocortin (POMC) mRNA and prolactin mRNA were determined by in situ hybridization. Immunohistochemistry was used to determine the percentage of cells that were immunopositive for ACTH (corticotrophs) or prolactin (lactotrophs). ACTH output was stimulated by CRH treatment at day 139 but not at day 129 of gestation, and cortisol attenuated this response. ACTH output by cells cultured with 10 nM E2 and 100 nM CRH, at 139 days of gestation, was greater than with CRH alone (p < 0.05). E2 did not affect basal ACTH output or ACTH output with any other treatment or levels of POMC mRNA. Prolactin output was not affected by E2 treatment. Bromocriptine significantly decreased prolactin output but not levels of prolactin mRNA. We conclude that E2 may affect CRH-stimulated fetal sheep pituitary corticotroph function late in gestation, but only within a narrow, physiological range of concentration.

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Maturation and Activation of Hypothalamic-Pituitary Adrenal Function in Fetal Sheep*

Challis

1989

Endocrine Reviews

272

129

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The progressive rise in the concentration of cortisol in the plasma of fetal sheep during late pregnancy arises from the sequential maturation of the fetal HPA axis. In addition, cortisol itself occupies a central role in accelerating this process through a series of feed-forward mechanisms. Before days 100-110 of pregnancy AVP appears to predominate over CRH as the major corticotropin-releasing factor in the fetus. Pituitary responsiveness to CRH increases progressively after day 100, and precedes maturation of fetal adrenal responsiveness to endogenous or exogenous ACTH. Cortisol accelerates the increase in the ratio of adult-fetal corticotropes in the fetal pituitary. In addition, cortisol modulates the mechanism by which ACTH activates fetal adrenal function, possibly through an action at the level of the ACTH receptor. Cortisol appears also to mediate the rise in fetal plasma CBG concentrations during late pregnancy, and may thereby alter the efficacy of the negative feedback process. In women, cortisol acts on the placenta to promote rather than to inhibit CRH output. CRH from the placenta may reach significant concentrations in the fetal circulation and augment the drive to fetal ACTH release. It may also act in a paracrine fashion to promote placental POMC gene expression. The importance of placental CRF and ACTH in the sheep is not yet apparent. These feed-forward loops establish a series of positive cascades that ensure concurrent rises in plasma ACTH and cortisol in the fetal circulation during late pregnancy. We suggest that this sequence leads to, and is broken by, the process of birth.

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Dose-dependent effects of arginine vasopressin on endocrine and blood gas responses of fetal sheep during the last third of pregnancy

Cited by 4 publications

References 12 publications

Activation of Fetal Hypothalamic-Pituitary Function and Birth

Activation of Fetal Hypothalamic-Pituitary Function and Birth

The effect of estradiol on output of adrenocorticotropin and prolactin by fetal sheep anterior pituitary cells

Maturation and Activation of Hypothalamic-Pituitary Adrenal Function in Fetal Sheep*

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