Search PubMed⌕ Search

Biomedical subjects

B G Miller

Publications and source records attributed to B G Miller.

At least 109 records · Page 6Linked to original sources

Uterine and placental growth: RNA and protein metabolism and steroid hormone receptor levels in the endometrium, whole uterus and cotyledons during pregnancy in the ewe.

Some aspects of uterine and placental growth have been examine during pregnancy in the ewe. Changes in vitro rates of protein synthesis, RNA: DNA and protein: DNA ratios and the tissue concentration of DNA in intercaruncular endometrium and caruncles (cotyledons between days 0 (oestrus) and 112 of pregnancy were compared with corresponding changes in the concentrations of high-affinity cytosol receptors for oestradiol and progesterone in whole uterus and caruncles/maternal cotyledons. Rapid growth of the intercaruncular endometrium between days 28 and 112 and of the developing cotyledons between days 28 and 84 occur in the presence of tissue levels of both steroid receptors that are extremely low in relation to the corresponding levels seen in the uterus at oestrus. If uterine responses to steroid hormones are regulated by the amounts of specific receptors present in the tissue, the results support the concept that uterine growth after day 28 of pregnancy results primarily from the physical stimulus of the growing concepts rather than from the actions of endogenous steroid sex hormones.

Animals↗

Do oestrogens regulate placental growth in the mouse?

Some effects of litter size, ovariectomy and oestradiol (E2) on placental growth were determined. In order to increase variation in litter size, some mice had one oviduct removed and the remainder were unilaterally ovariectomized 3-4 weeks prior to mating. Thus after mating mice became unilaterally pregnant. Growth was examined qualitatively by measuring changes in placental DNA, protein, RNA : DNA ratios and in vivo incorporation of [5-3H]uridine into RNA. Spontaneous placenta hyperplasia due to low litter size occurred to an equal extent in intact mice and mice which were ovariectomized on day 10 of pregnancy and given 1.0 mg progesterone (P) and 10 ng E2 daily. Ovariectomy on day 10 increased the incorporation of [5-3H]uridine into placenta RNA on day 16 in mice with six or more foetuses. When mice were ovariectomized on day 5 and given 1.0 mg P and 10 or 60 ng E2 daily to maintain gestation, rates of placental growth remained similar to the rate in control, intact mice. The results suggest that, unlike the case in the rat, oestrogens do not regulate placental growth in the mouse.

Animals↗

Effects of progesterone on the oestrogen-stimulated uterus: a comparative study of the mouse, guinea pig, rabbit and sheep.

To examine more closely the anti-oestrogenic action of progesterone (P), its effect on various parameters in the 17 beta-oestradiol (E2)-primed uterus of the mouse, guinea pig, rabbit and ewe was studied. Changes in uterine wet weight, rate of in vitro protein synthesis, protein : DNA and RNA : DNA ratios, peroxidase activity and the level of cytosol receptors for E2 and P were measured. Considerable between-species differences in the effect of P on these parameters were observed. The anti-uterotrophic action was greater in the mouse than in the guinea pig and was not seen in the rabbit or ewe. P inhibited protein synthesis in the mouse, was without significant effect in the guinea pig and was mildly stimulatory in the rabbit and ewe. Inhibitory effects on protein : DNA and RNA : DNA ratios were substantial in the mouse, minor in the guinea pig and absent in the rabbit and ewe. Peroxidase activity was decrease in the mouse and guinea pig, essentially lacking in the rabbit and not detectable in the ewe. In all species the level of both oestrogen and progesterone cytosol receptors was decreased, although the effect on the E2 receptor was less marked in the ewe. The results indicate that in the species studied an effect of P on the replenishment of the E2 receptor is not necessarily associated with other anti-oestrogenic actions of P and argue against the concept that initial anti-oestrogenic actions of P are mediated via a specific effect on such replenishment.

Animals↗

The relationship between protein turnover and energy balance in lean and genetically obese (ob/ob) mice.

1. Groups of lean and genetically obese (ob/ob) mice were adapted to varying energy intakes and the rates of total protein turnover in liver, gut and kidney were measured. 2. Lean mice gained less weight when fed above maintenance and lost less weight when fed below maintance than obese mice. 3. Hepatic protein turnover (mg/d) was sigmoidally related to digestible energy intake in lean mice but showed no significant changes with dietary intake in obese mice. 4. The changes in protein turnover resulted from changes in both the half-lives of protein synthesis and catabolism and in tissue protein content. 5. In the lean mice, protein turnover in kidney and gut was not significantly changed with increasing energy intake until the highest level was reached. 6. The findings suggest that protein turnover may be an important cycle for the regulation of energy balance in mice and that this cycle is impaired in the genetically obese (ob/ob) mice.

Animals↗

A new technique for measuring protein turnover in the gut, liver and kidneys of lean and obese mice with [3H] glutamic acid.

1. We have measured the incorporation of an intraperitoneal injection of [3H] glutamate into the protein of the gut, liver and kidney of lean and obese siblings of the genetically obese mouse. 2. Recycling of the 3H was minimized by using glutamate labelled at the C-2 position. Loss of label from the amino acid pool by transamination and deamination was rapid, with a half-life of 4 h. 3. In tissue protein the amino acid showing the highest 3H radioactivity was glutamate. 4. The half-lives for protein synthesis and catabolism were calculated from the decay curves of both specific and total radioactivity of [3H] glutamate in tissue protein. No significant differences were found between kidney, liver and gut in lean and obese mice.

Animals↗

Effects of ovarian hormones on foetal and placental growth in the mouse.

The effects of ovariectomy and treatment with progesterone and oestradiol on foetal and placental growth were examined. The occurrence of cellular hypertrophy and hyperplasia in the placenta in response to treatments was determined by measuring protein, DNA and RNA:DNA ratios. In control mice, which had not been ovariectomized, the daily administration of 0.01-2.56 microgram oestradiol on days 10-15 of pregnancy caused only small decreases in the number of live foetuses and foetal and placental weights on day 16. When mice were ovariectomized on day 10, gestation was maintained by administering 5 mg progesterone daily, but terminated when only 1 mg progesterone was given daily. However, when ovariectomized mice receiving 1 mg progesterone were also given 0.01 microgram oestradiol on days 10-15, gestation was maintained and the number of live foetuses and foetal and placental weights on day 16 were normal. Increasing the daily dose of oestradiol up to 2.56 microgram in mice receiving 1 mg progesterone on days 10-15 had no effect on foetal and placental growth. In contrast, the daily administration of 0.64-2.56 microgram oestradiol to ovariectomized mice receiving 5 mg progesterone on days 10-15 terminated gestation in some mice and considerably reduced the number of live foetuses and foetal and placental weights in those mice which remained pregnant on day 16. None of the treatments increased protein DNA or the RNA:DNA ratio in the placenta to levels above those seen in control mice. The results are discussed in relation to ovariectomy-induced placental overgrowth in the rat.

Animals↗

Oestradiol and progesterone: soluble receptor levels and metabolism in the uterus of the ovariectomized ewe.

Ovariectomized ewes received injections designed to mimic to some extent oestradiol and progesterone secretion during early pregnancy (maintenance progesterone), during oestrus (oestrous oestradiol) and during the luteal phase of the previous cycle (priming progesterone). The animals were killed at times equivalent to 1, 4 or 7 days after oestrus in those animals which had received oestrous oestradiol. The level of soluble oestradiol and progesterone receptors in whole uterus, and [3H]oestradiol and [3H]progesterone metabolism by uterus minces were measured. Oestradiol receptor level was highest on day 1 in those animals receiving oestrous oestradiol with no significant effect at any stage of the inclusion or omission of priming or maintenance progesterone. Progesterone receptor level was also high on day 1 in those animals receiving oestrous oestradiol with high levels maintained to day 4. Again, inclusion of priming or maintenance progesterone was without effect. In animals not receiving oestrous oestradiol the level of both receptors was uniformly low. Metabolism of [3H]oestradiol was low and not affected by treatment. [3H]Progesterone metabolism, although more variable, was also low and not affected by treatment.

Animals↗

Hormone receptor levels and hormone, RNA and protein metabolism in the genital tract during the oestrous cycle of the ewe.

The concentrations of soluble oestradiol and progesterone receptor proteins and several metabolic activities were measured in the genital tracts of ewes killed on Days 0 (oestrus), 2, 5, 10 or 14 of the oestrous cycle. In caruncular endometrium and in whole uterus the concentrations of oestradiol receptor (pmol steroid bound/mg tissue DNA) were highest at oestrus and declined steadily thereafter to minimal values at Day 14. The concentrations of progesterone receptor were highest on Days 0-5, then declined to low levels on Day 10-14. There was little metabolism of either [3H]oestradiol or [3H]progesterone in minces of whole uterus and with either steroid the pattern of metabolism did not change at any stage of the cycle. The in-vivo rates of synthesis of protein in caruncular endometrium and in isthmic oviduct were highest at or shortly after oestrus (Days 0-2), then declined to low levels on Days 10-14. RNA:DNA ratios in these two tissues were also greatest at oestrus and subsequently fell to minimal values by Day 14. The results are discussed in relation to ovarian secretion of oestradiol and progesterone during the oestrous cycle of the ewe.

Animals↗