Ebook Steroid Hormone Changes In Pregnant Rats
Undernutrition is known to affect plasma levels of many hormones. Several of the hormones that regulate metabolism, such as insulin, glucagon, growth hormone, and thyroid hormone, are known to undergo adaptive changes in nonpregnant individuals subjected to undernutrition. Furthermore, several studies have explored how undernutrition, especially fasting, alters these metabolic regulators in pregnant subjects. These studies have generally demonstrated that metabolic adaptation to starvation occurs more rapidly during pregnancy.
Pregnancy, however, is characterized by the elaboration of steroid hormones (estrogens and progesterone), which, though present in nonpregnant subjects, show marked increases during gestation. Many biological processes are influenced by these steroids and they may well play a fundamental role in maternal physiologic adaptations to pregnancy, adaptations that are essential for normal pregnancy outcome. Although physiological adaptations are dampened by undernutrition, it is not known whether hormonal changes mediate these effects, or whether the levels of these hormones are altered differentially by different types of maternal undernutrition. In humans, it has been found that women with high progesterone levels have a higher mean placental weight and a tendency for high fetal weight. Since the placenta is the main source of progesterone in humans, however, it is possible that improved growth is responsible for increased progesterone and not the converse. Since fetal growth and viability depend on appropriate maternal adjustments, it would be valuable to know if changes in gestational hormones, acting to affect maternal adjustments to pregnancy, contribute to the reduced fetal growth associated with undernutrition.
Although little is known about the effect of nutrition on gestational production of estrogens and progestins, several findings are suggestive. For example, in nonpregnant subjects, undernutrition is known to alter the levels of several of the hormones essential for sexual functions. Thus amenorrhea and infertility are the result of severe undernutrition, such as is observed in anorexia nervosa and in severe, primary starvation. Moreover, in rats fed a zero protein diet throughout gestation, spontaneous resorption of fetuses could be largely prevented by the administration of estrone and progesterone, although it was not determined whether the diet had lowered blood levels of these hormones. Other workers studying early gestation (to day 13 or 15) in rats have shown that plasma progesterone is significantly reduced in rats fed zero protein diets and is also somewhat lower in rats fed 6% protein . In rats restricted 75% during the first ten days of pregnancy, administration of a constant amount of progesterone daily, concurrent with the restriction, appears to alter the pattern of fetal growth. In humans, where infant weight has been correlated with plasma volume expansion, urinary estriol excretion in the first two trimesters showed a tendency to be reduced in women bearing low weight infants (<25th percentile). In addition, it has been reported that undernourished, pregnant Indian women excrete a reduced amount of urinary estrogens. An increased estrogen excretion and an increase in infant birth weight were observed when these women were hospitalized and given better food and bed rest during late gestation. In order to be excreted in the urine, however, estrogen must be conjugated by the liver. It is conceivable that undernutrition reduces urinary levels by reducing conjugation, in which case blood levels could be increased rather than decreased by undernutrition. Furthermore, estriol, a major urinary estrogen, is produced by the fetal-placental unit. Thus, increased production could be the result, not a cause, of increased conceptus growth.
We have previously proposed that inadequate maternal plasma volume expansion and the associated reduction in uterine blood flow resulting from undernutrition during pregnancy may be a major determinant of the associated fetal growth retardation. We have documented that low protein feeding, food restriction or fasting can prevent the normal expansion of plasma volume during pregnancy in the rat. These studies have shown that the decrement originally observed in maternal plasma volume at term, may be observed by day 19 of pregnancy as well. Since estrogen and progesterone increase total body water and reduce vascular tone, it is conceivable that the marked increase in plasma volume occurring during gestation is partly mediated by these hormones. If so, undernutrition would be expected to alter the levels of these hormones, since undernutrition largely prevents this plasma volume expansion.
The present study was designed to determine if the levels of progesterone or estrogens were altered by undernutrition during pregnancy. In addition, the relationship of these hormones to maternal plasma volume expansion was also explored. Because we had shown that food restriction, low protein feeding, and fasting all induced alterations in maternal plasma volume as well as affecting fetal growth, all three models were studied for their effects on maternal hormone levels.
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