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Biomedical subjects

T M Mills

Publications and source records attributed to T M Mills.

At least 55 records · Page 3Linked to original sources
PubMed1987

The effects of progesterone on follicular growth in the rabbit ovary.

Studies were undertaken to measure the growth of follicles in the rabbit ovary during periods of elevated blood levels of progesterone. The progestin was increased in the blood by pregnancy or by implantation of progesterone pellets, which raised blood progesterone to near the levels measured during pregnancy. After 1, 2, 3, or 4 weeks of pregnancy or progesterone-pellet treatment, follicles of 1.0 mm external diameter or greater were dissected out of the ovaries and their external diameters were measured; then, each follicle was extracted for measurement of estradiol content. Blood levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in these animals as well. Follicles up to 2.5 mm in diameter were found in the ovaries of nonpregnant and untreated animals while 1.8 mm was the maximal size found during pregnancy or progesterone-pellet treatment. Furthermore, both in pregnant and in progesterone-treated rabbits, the follicular estradiol content and concentration were significantly suppressed compared to follicles from untreated rabbits. The progesterone pellets had no major effect on the levels of LH and FSH in the blood; the concentration of these gonadotropins in the progesterone-treated rabbits was virtually identical to levels previously measured in the blood of pregnant animals. The results of these studies indicate that progesterone exerts an inhibitory action on follicular development and steroidogenic function in the rabbit ovary. The progesterone action appears to be exerted directly on the ovary and is not indirect, by way of an inhibition of gonadotropin secretion.

Animals↗
PubMed1986

Stimulation of sulfated-proteoglycan synthesis by forskolin in monolayer cultures of rabbit articular chondrocytes.

Forskolin, a plant cardiotonic diterpene, stimulated proteoglycan biosynthesis by chondrocytes in monolayer culture. The quantitative increase in proteoglycans was dependent on the concentration of forskolin, but was relatively independent of the presence of serum. At forskolin concentrations that stimulated proteoglycan synthesis, a significant stimulation of adenylate cyclase and cAMP was also measured. The quantitative increase in proteoglycans was characterized, qualitatively, by an increased deposition of newly synthesized proteoglycan in the cell-associated fraction. An analysis of the most dense proteoglycans (fraction dA1) in the cell-associated fraction showed that more of the proteoglycans eluted in the void volume of a Sepharose CL-2B column, indicating that an increased amount of proteoglycan aggregate was synthesized in forskolin-treated cultures. The proteoglycan monomer dA1D1 secreted into the culture medium of forskolin-stimulated cultures overlapped in hydrodynamic size with that of control cultures, although cultures stimulated with forskolin and phosphodiesterase inhibitors produced even larger proteoglycans. The hydrodynamic size of 35SO4 and 3H-glucosamine-labelled glycosaminoglycans isolated from the dA1D1 fraction of the culture medium was greater in forskolin-treated chondrocytes, especially from those in which phosphodiesterase inhibitors had been added. These results indicated that forskolin, a direct activator of chondrocyte adenylate cyclase mimicked the effects of cAMP analogues on chondrocyte proteoglycan synthesis previously reported. These results implicate activation of adenylate cyclase as a regulatory event in the biosynthesis of cartilage proteoglycans, and more specifically in the production of hydrodynamically larger glycosaminoglycans.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Dissociation of copulation from ovulation in pregnant rabbits.

Experiments were designed to determine why copulation in the pregnant rabbit does not terminate pregnancy while treatment with ovulatory doses of luteinizing hormone (LH) human chorionic gonadotropin (hCG) or luteinizing hormone-releasing hormone (LHRH) is known to do so. Pregnant rabbits (Day 8) were mated or were injected with hCG (25 IU/doe) or LHRH (1, 10 micrograms/kg). Serial blood samples were collected over the next 72 h and analyzed for content of LH, follicle-stimulating hormone (FSH) and progesterone. At sacrifice, uteri and ovaries from these animals were examined for viability of the embryos and for signs of recent ovulation. Injection of hCG or LHRH into pregnant animals led to ovulation and to patterns of LH, FSH and progesterone secretion like those which precede ovulation in estrous rabbits. However, mating the pregnant does did not lead to ovulation or to any changes in the circulating hormones. To investigate whether the elevated levels of progesterone during pregnancy were responsible for the dissociation of coitus from ovulation, nonpregnant rabbits were injected with progesterone (2 mg/kg) and then mated or injected with hCG or LHRH. In virtually every respect, the numbers of ovulations and the patterns of hormone secretion in the progesterone-treated, nonpregnant rabbits mimicked those observed in the 8-day pregnant animals; injection of hCG or LHRH caused ovulation and hormonal surges while hCG caused ovulation only. Mating did not lead to ovulation or any change in blood levels of LH, FSH or progesterone. Taken together, the results show that the elevated circulating levels of progesterone, characteristic of pregnancy, are probably responsible for the dissociation of copulation from gonadotropin release in pregnant rabbits.

Animals↗
PubMed1984

In-vivo and in-vitro steroidogenic activity of post-ovulatory ovarian follicles of the rabbit.

Pseudopregnancy was induced in rabbits by injection of 50 i.u. hCG into the lateral ear vein. Blood was collected on Days 0, 1, 2 and 6 after hCG from the lateral ear vein and, in some studies, from the ovarian vein as well. Ovaries were collected on Days 0, 1, 2 or 6 after hCG injection, and follicles (greater than 0.8 mm diam.) were obtained by microdissection. Concentrations of oestradiol-17 beta, testosterone and progesterone in blood and follicular homogenates were measured by RIA. Follicular steroidogenesis was increased significantly on Day 6 after ovulation, at the time when the corpus luteum transforms into an oestrogen-dependent tissue. The ability of developing post-ovulatory follicles to secrete steroids in vitro in response to a gonadotrophic stimulus also increased over this same time interval. Follicular oestradiol production on Days 1 and 2 of pseudopregnancy may synergize with the post-ovulatory secretion of FSH to promote further follicular growth in the pseudopregnant rabbit.

Animals↗
PubMed1983

Estimation of molecular parameters of the endogenous inhibitor to progesterone--receptor binding in rat trophoblast.

This study was undertaken to investigate molecular properties of an endogenous substance which inhibits progesterone--receptor binding. The inhibitor was isolated from the cytosol of rat trophoblast by ammonium sulfate precipitation. Further purification was achieved by gel filtration and sucrose density gradient centrifugation. These techniques revealed that the inhibitor had a Stokes radius of 2.8 +/- 0.1 nm and an s of 4.9 +/- 0.2. For a protein exhibiting normal density and solvation, these parameters indicated that the inhibitor molecule has a mol. wt of 56,000 +/- 2000 g/mol and a frictional coefficient of 1.11 +/- 0.01. In order to obtain an additional independent estimate of molecular weight, the migratory pattern of the inhibitor was studied on SDS-polyacrylamide gels after identification and purification by polyacrylamide gel electrophoresis. The inhibitor-active fraction was resolved into two principle bands (Band 1 and 2) by SDS-gel electrophoresis having mol. wt of 59,000 +/- 700 g/mol and 51,000 +/- 300 g/mol (n = 6), respectively. The molecular weight thus determined was in excellent agreement with the value obtained by calculation. Thus, molecular parameters of the inhibitor indicate that it is a very symmetrical molecule of approx. 56,000 mol. wt. Characterization of the molecular properties of the inhibitor substance should facilitate future studies concerning the biological significance of this molecule and its role in progesterone--receptor binding interactions.

Animals↗
PubMed1983

Effects of castration and estradiol treatment on the postovulatory secretion of follicle-stimulating hormone in the mated rabbit.

The effects of castration on the postovulatory secretion of follicle-stimulating hormone (FSH) was measured in mated rabbits. When ovaries were removed at 12 or 18 h postcoitum, FSH increased within 24 h of surgery but without evidence of the previously observed pattern of FSH secretion in the postovulatory period. To prevent the postcastration rise in FSH, various doses of estradiol were injected into does castrated 12 h after mating. Two micrograms estradiol/kg, given daily, was found to prevent the postcastration rise of FSH but was not sufficient to suppress the postovulatory secretion of FSH in intact animals. The postovulatory pattern of FSH release was disrupted in does castrated at either 12 or 18 h postcoitum despite adequate estradiol replacement therapy. Furthermore, in chronically castrated does treated with estradiol (2 micrograms/kg per day), neither mating nor human chorionic gonadotropin (hCG) injection elicited any change in blood FSH levels even though both treatments have been previously found to cause a postovulatory FSH surge. The results of these studies indicate that the ovary, by way of some ovarian secretion, is required for the postovulatory secretion of FSH in the rabbit. The necessary ovarian factor does not appear to be estradiol.

Animals↗
PubMed1983

Is the postovulatory release of follicle-stimulating hormone in the rabbit mediated by luteinizing hormone-releasing hormone?

Studies were performed to determine whether the postovulatory secretion of FSH in the rabbit is an LHRH-mediated event. Does were mated and then injected at 12 and 18 h postcoitum with pentobarbital (30 mg/kg BW), an agent known to block endogenous LHRH release. The injection of this barbiturate had no measurable effect on the postovulatory FSH secretion pattern. Administration of the LHRH antagonist [Ac-D-p-C1-Phe1,2, Phe3, D-Arg6, D-Ala10]LHRH (0.5 mg/doe) prevented all gonadotropin release in response to LHRH injection (10 micrograms/kg BW). When this same dose of the antagonist was injected at 18 h postcoitum, the postovulatory FSH secretion pattern was unaffected. Finally, to prove that the pituitary was sensitive to LHRH at 18-h postcoitum, LHRH (10 micrograms/kg BW) was injected into rabbits mated 18 h earlier; this treatment led to a marked increase in FSH secretion showing that the pituitary is responsive to LHRH at this time. The results of this study show that two drugs which block LHRH-mediated gonadotropin release have no effect on the postovulatory secretion of FSH and support the concept that this episode of FSH secretion occurs via a pathway which does not include the hypothalamic secretion of LHRH.

Animals↗
PubMed1982

Effects of ketamine-xylazine anesthesia on blood levels of luteinizing hormone and follicle stimulating hormone in rabbits.

The effect of injection of an anesthetic dose of ketamine (70mg/kg) followed by xylazine (5mg/kg) on blood levels of luteinizing hormone and follicle stimulating hormone was measured in female rabbits. The drug combination caused a measurable suppression of follicle stimulating hormone levels in both castrated does and during the postovulatory follicle stimulating hormone surge in mated rabbits. Blood luteinizing hormone was low in these two animal model systems and was not further suppressed by ketamine-xylazine injections. When mated rabbits were injected with the drugs immediately postcoitum, ovulation and the preovulatory surge of luteinizing hormone and follicle stimulating hormone failed to occur in two of six treated animals. The results of these studies showed that ketamine-xylazine injections suppressed certain episodes of gonadotropin release in the female rabbit. However, the suppression was transitory and without apparent permanent effect.

Anesthesia, General↗
PubMed1979

Accumulation of norethindrone and individual metabolites in human plasma during short- and long-term administration of a contraceptive dosage.

Blood levels of free, sulfate, and glucuronide conjugates of norethindrone (NE) and its ring A reduced metabolites 17alpha-ethynyl-5beta-estrane-3alpha, 17beta-diol and 17alpha-ethynyl-5alpha-estrane-3alpha, 17beta-diol were measured in a female volunteer who received six consecutive daily doses of 2.5 mg. of NE and in four female volunteers undergoing chronic treatment with Orthonovum 2 mg. (2 mg. of NE and 0.1 mg. of mestranol [ME]). The blood levels were quantified by gas chromatograph-mass spectrometry. During treatment for 6 days with 2.5 mg. of NE daily, the 3 hour blood levels of NE and the ring A reduced metabolites increased in a stepwise fashion. During long-term treatment the concentrations of NE, NE sulfate, and the conjugates of the ring A reduced metabolites were seen to build up to a peak at approximately the midpoint of the treatment phase of each cycle, and drop to near baseline during the time when no drug was administered. Individuals varied as to their tendency to accumulate the drug and metabolites, and as to the relative proportion of metabolites formed.

Adult↗