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Biomedical subjects

T M Mills

Publications and source records attributed to T M Mills.

At least 73 records · Page 4Linked to original sources
PubMed1976

Metabolism of oral contraceptive drugs. The formation and disappearance of metabolites of norethindrone and mestranol after intravenous and oral administration.

Previous studies from this laboratory reported that 3H-labeled metabolites with half-lives of more than 24 hours may remain in the plasmaa of women receiving an intravenous injection of 3H norethindrone or 3H mestranol. To confirm the presence of these metabolites, blood samples were collected for five days after injection of 3H norethindrone or 3H mestranol; 3H representing metabolites of norethindrone disappeared with half-life values of 42 to 84 hours (mean 67 hours), while 3H representing metabolites of mestranol declined with an average half-life of 45 hours (range 37 to 65 hours). When the 3H-labeled drugs were administered orally, metabolites of similar half-life were formed. Because these compounds exist for several days after a single administration and since oral contraceptive drugs are normally taken daily, the possiblity of the accumulation of 3H in the plasm of women receiving several consecutive doses of 3H norethindrone was investigated. The results of this study show a stepwise accumulation of the 3H metabolites when 3H norethindrone was administered in six daily oral doses. However, the 3H levels declined from the peak on the sixth and last day of the treatment at a rate equivalent to those previously measured after intravenous or oral administration.

Administration, Oral↗
PubMed1976

Amino acid transport in follicles isolated from the rabbit ovary.

The model amino acid alpha-aminoisobutyric acid (AIB) has been used to investigate amino acid transport in follicles isolated from rabbit ovaries. LH markedly increased AIB transport, while incubation with FSH, cAMP or dbcAMP failed to increase the process. Several kinds of inhibitors have been utilized to characterize follicular AIB transport as an energy dependent process and apparently independent of follicular steroidogenesis. The rates of AIB efflux from preloaded follicles were measured in the presence and absence of LH; the rate measurements suggest that only the rate of entry of AIB into follicular cells is stimulated by the gonadotropin. Further experiments used inhibitors of RNA and protein synthesis to examine the relationship between AIB transport and the synthesis of macromolecules. Whereas blocking RNA synthesis suppressed the LH effect on AIB transport, inhibitors of protein synthesis increased the rate of AIB movement into follicles. The in vitro transport of AIB was also studied in follicles isolated 2 hr after mating and in ovulated follicles which were obtained 12 h after coitus. AIB transport rate showed a rise following mating but fell to less than precoital rates in ovulated (12 h) follicles. Transport in both 2 and 12 h follicles proved unresponsive to LH stimulation. Taken together, these studies suggest that AIB transport in isolated ovarian follicles is a LH-sensitive, energy-dependent process. Although AIB transport changes in a pattern qualitatively similar to that previously reported for postcoital protein synthesis, LH stimulation of the two processes may be via different mechanisms.

Aminoisobutyric Acids↗
PubMed1975

Effect of luteinizing hormone and cyclic adenosine 3',5'-monophosphate on steroidogenesis in the ovarian follicle of the rabbit.

Mature ovarian follicles have been isolated from estrus rabbits and the effects of gonadotropin and cyclic AMP on steroidogenesis in this tissue determined. Gonadotropins used include LH, FSH, and prolactin; follicular levels of progesterone, 17-hydroxyprogesterone, testosterone and 17beta-estradiol in all experiments were quantitated by radioimmunoassay. Incubation of follicles with LH in concentrations ranging from 0.05 to 50 mug/ml medium yielded increases in the total ng steroid/follicle. Five mug LH/ml gave a maximal response with no further increase in steroid concentration when the LH was raised to 50 mug/ml. Prolactin had no effect on follicular steroidogenesis while the stimulatory action of a FSH preparation could only be partially attributed to LH contamination. Cyclic AMP also proved to be a potent stimulatory agent in follicular steroidogenesis with maximal increases at 20 mumoles/ml and a decline in the ng steroid/follicle when cyclic AMP was raised to 30 and 40 mumoles/ml. The effects of LH and cyclic AMP proved to be nonadditive; incubation of follicles simultaneously with 5 mug LH/ml and 20 mumoles cyclic AMP/ml yielded steroid concentrations which were no different than levels following incubation with either agent alone. Taken together, these results demonstrate that both LH and cyclic AMP cause increases in radioimmunoassayable steroid in the rabbit follicle in vitro and that LH probably acts by way of a cyclic AMP intermediate.

Animals↗
PubMed1975

Protein and RNA synthesis in follicles isolated from rabbit ovaries.

The in vitro synthesis of protein and RNA in follicles from mated and unmated rabbits has been studied by measuring precursor incorporation. Radioactive methionine incorporation into follicular proteins showed a transitory rise following coitus but fell to precoital levels in ovulated follicles. LH, FSH, and cyclic AMP all exerted an acute stimulatory action on the incorporation of amino acids into proteins by follicles from unmated rabbits. Radioactive uridine incorporation into follicular RNA showed the same temporal pattern of postcoital rise followed by a decline in incorporation rates in the period around ovulation. In acute incubations, FSH and cyclic AMP stimulated RNA synthesis; LH was without acute action on this process. The results of these studies suggest that a wave of follicular protein and RNA synthesis precedes ovulation and may be partly related to the preovulatory surge in gonadotropins.

Animals↗