Search Results
You are looking at 11 - 20 of 64 items for
- Author: L. MARTIN x
- Refine by access: All content x
Search for other papers by BARBARA FAGG in
Google Scholar
PubMed
Search for other papers by L. MARTIN in
Google Scholar
PubMed
The oestrogen content of the separated uterine tissues (epithelium, stroma and myometrium) of mice was determined at various times between 1 and 24 h after administration of [3H]oestradiol or [3H]oestriol either subcutaneously or directly into the uterine lumen. After subcutaneous injections, the oestrogen levels of both the stroma and myometrium declined steadily from a maximum at 2–4 h after injection and more oestradiol than oestriol was always present. In contrast, the epithelium contained more oestriol than oestradiol and the levels of both hormones remained fairly constant over the period studied. However, a smaller percentage of the epithelial oestriol than of oestradiol was associated with the nuclear fraction. On the contrary, after intraluminal injections, the oestrogen content of all the separated tissues decreased from a maximum at 1–2 h and more oestradiol than oestriol was retained in all cases. A high proportion of the total epithelial content of both oestrogens was recovered in the nuclear fraction.
The uterine proliferative response after intraluminal injection of oestradiol or oestriol was qualitatively and quantitatively similar to that observed after subcutaneous injection of hormone, indicating that the efficacy of the oestrogens is not markedly dependent on the route of administration. These data support current concepts of oestrogen action in the uterus but indicate that studies of the whole organ may not, in all respects, be extrapolated to the individual target tissue. The importance of nuclear hormone levels as the determinant of the oestrogenic response is also emphasized.
Search for other papers by A. Lipton in
Google Scholar
PubMed
Search for other papers by A. Vinijsanun in
Google Scholar
PubMed
Search for other papers by L. Martin in
Google Scholar
PubMed
ABSTRACT
The non-steroidal antioestrogen tamoxifen (trans-1-(4-β-dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene), widely used in the treatment of breast cancer, and its oestrogenic cis-isomer rapidly inhibited contractile responses of isolated rat myometrium to supramaximal concentrations of oxytocin (1·28 × 10−6 mol/l). Both compounds were effective at concentrations comparable with the plasma concentrations of tamoxifen reached in therapy (i.e. 5 × 10−7to 5 × 10−6 mol/l). Inhibition was too rapid in onset ( < 3 min) to involve changes in RNA transcription and protein synthesis, and was not prevented or reversed by the addition of oestradiol to the bath. We conclude that the inhibition did not involve the classical oestrogen receptor pathway. Oestradiol-17β at concentrations above 10−6 mol/l also inhibited the myometrium and potentiated the effects of the antioestrogens. Our experiments suggest that the antioestrogens and oestradiol act via a similar route with tamoxifen having an equilibrium affinity approximately tenfold greater than that of oestradiol.
J. Endocr. (1984) 103, 383–388
Search for other papers by R. M. DAS in
Google Scholar
PubMed
Search for other papers by L. MARTIN in
Google Scholar
PubMed
Oestradiol stimulates uterine luminal epithelial cells of ovariectomized mice to pass through two rounds of cell division in quick succession (Das, 1972; Martin, Finn & Trinder, 1973). Progesterone injected with the oestrogen blocks entry of some cells into the first round of proliferation without affecting G1, S or G2 in the remainder, but blocks entry of these cells into the second round. This suggested that cells were only sensitive to progesterone in early G1 (Martin, Das & Finn, 1973). In the present experiment we attempted to delineate the sensitive period in greater detail.
Randomly bred albino mice were ovariectomized and primed as described previously (Das, 1972). Five days after priming they were separated into ten groups of three. All were given 50 ng oestradiol subcutaneously in 0·1 ml arachis oil at 0 h and 25 μCi [3H]thymidine ([3H]Thd; sp. act. 5 Ci/mm, Amersham) intraperitoneally
Search for other papers by C. A. FINN in
Google Scholar
PubMed
Search for other papers by L. MARTIN in
Google Scholar
PubMed
Department of Physiology, Royal Veterinary College, Royal College Street, London, NW1 OTU, and *Imperial Cancer Research Fund, Lincolns Inn Fields, London, WC2A 3PX
(Received 8 June 1976)
Although the endometrial glands form a prominent part of the uterus of rodents, surprisingly little is known of the factors controlling their secretion, or indeed of the function of the secretion. During pregnancy the glands proliferate on the third day after mating in response to the high levels of oestrogen secreted during pro-oestrus (Finn & Martin, 1967, 1973). Secretion, however, does not become apparent in the lumina of the glands until day 6 of pregnancy. The extent of secretion is difficult to quantitate because it is not possible to collect it. However histological sections, especially after staining with the periodic acid-Schiff's (PAS) technique, reveal clearly the presence of a mucopolysaccharide substance in the lumina of the glands so that an approximate subjective assessment
Search for other papers by L. MARTIN in
Google Scholar
PubMed
Search for other papers by C. A. FINN in
Google Scholar
PubMed
SUMMARY
Progesterone treatment significantly altered the response of the mouse uterus to oestradiol-17β. Oestradiol given alone produced many mitoses in the luminal and glandular epithelia but not in the connective tissue stroma. After treatment with progesterone this pattern was reversed and oestradiol produced many mitoses in the stroma but few in the epithelia. Production of stromal cell division was influenced by the dose of progesterone and by the period of treatment; a single day of treatment greatly reduced the numbers of epithelial mitoses produced by oestradiol but did not greatly increase stromal mitosis. At least 3 days' treatment was necessary for a maximal stromal response.
Doses of oestradiol sufficient to inhibit implantation and deciduomata production did not reverse the stromal response but did overcome, in part, the progestational suppression of epithelial mitosis, producing large numbers of mitoses in the luminal but not in the glandular epithelium.
Search for other papers by L.-Å. IDAHL in
Google Scholar
PubMed
Search for other papers by J. M. MARTIN in
Google Scholar
PubMed
Destruction of the ventro-medial region of the hypothalamus results in hyperinsulinism (Hales & Kennedy, 1964; Frohman, Bernadis, Schnatz & Burek, 1969) and enlargement of the islets of Langerhans (Coleman & Hummel, 1970; Han, Yu & Chow, 1970), demonstrable a few hours after making the lesion (Martin & Bouman, 1971). These changes are progressive and independent of the ensuing hyperphagia (Han et al. 1970; Martin & Bouman, 1971). Whether this direct hypothalamic effect was mediated by the autonomic nervous system or by a humoral factor was not determined.
We investigated the latter possibility by exposing isolated islets of Langerhans, dissected from mouse pancreas (Hellman, 1970), to the effect of pieces of hypothalamus from either the medial or lateral region. The islets were located in a 10 μl chamber and perfused with Krebs-Ringer bicarbonate buffer supplemented with either 5·6 or 16·7 mm-glucose (Idahl, 1970). An additional chamber containing the hypothalamic tissue - or
Search for other papers by C. A. FINN in
Google Scholar
PubMed
Search for other papers by L. MARTIN in
Google Scholar
PubMed
SUMMARY
Estimates were made of the number and distribution of cells undergoing division in the mouse uterus during the first 6 days of pregnancy. There was a spectacular change in the distribution of mitoses between days 3 and 4. On day 3 large numbers of mitoses were present in the luminal and glandular epithelium, with few in the stroma, whereas on days 4 and 5 very large numbers were present in the stroma with few in the epithelia.
On day 6 and late on day 5, in the vicinity of a blastocyst, the area containing decidual cells was free of mitoses. Many mitoses were found in the stroma immediately outside this area and there was evidence that the rate of division here was greater than in segments of the uterus unstimulated by a blastocyst.
Search for other papers by L. MARTIN in
Google Scholar
PubMed
Search for other papers by C. A. FINN in
Google Scholar
PubMed
Oestradiol-17β stimulates mitosis in the luminal epithelium but not in the connective tissue stroma of the uterus of the mouse. Treatment with progesterone reverses this pattern so that oestradiol stimulates mitosis in the stroma but not in the epithelium. A single injection of progesterone suppresses the epithelial response to oestradiol, but does not induce a stromal response. This occurs only after three daily injections of progesterone (Martin & Finn, 1968). The following experiment was carried out to determine if all three progesterone injections were necessary, or if a stromal response to oestradiol might develop 3 days after a single injection.
Albino mice were ovariectomized 2 weeks before the start of the experiment. They were not primed with oestradiol (Martin & Finn, 1968) since there is evidence that uterine sensitivity to the hormones changes significantly in the days after priming (unpublished results). The hormones were given s.c. in 0·05 ml. arachis
Search for other papers by C. A. FINN in
Google Scholar
PubMed
Search for other papers by L. MARTIN in
Google Scholar
PubMed
SUMMARY
The distribution of cell division in the tissues of the mouse uterus changes in a characteristic manner during the first few days of pregnancy due to changes in the secretion of ovarian hormones. Pregnant mice were ovariectomized at various times and attempts made to reproduce the pattern of cell division with exogenous hormones. The schedule of hormone injections producing a pattern of uterine mitoses which most closely approached that of pregnancy suggested that secretion of both oestrogen and progesterone started about 48 hours after mating and continued, possibly increasing, until after implantation had started. This conflicts with the oestrogen surge hypothesis. Further experiments were carried out to determine the optimum hormone treatment schedules for sensitivity to induction of the oil decidual cell reaction. Multiple small doses of oestradiol allowed the production of greater deciduomas than a single dose, thus again suggesting that the oestrogen surge hypothesis may not be correct.
Search for other papers by C. A. FINN in
Google Scholar
PubMed
Search for other papers by L. MARTIN in
Google Scholar
PubMed
SUMMARY
Priming of ovariectomized mice with 0·1 μg. oestradiol-17β for 3 days modified the subsequent cellular response of the uterus to oestrogen and progesterone. A single dose of oestradiol-17β (0·02 μg.), or progesterone (1 mg.), or of both hormones given simultaneously, stimulated mitosis in the epithelial cells of the endometrium (although not in the stromal cells). However, the same hormones administered to primed mice stimulated considerable stromal cell division and reduced epithelial mitosis. The maximal effect was found when both hormones were given on the 4th day after the end of priming. It is suggested that the priming of the uterus by oestrogen secreted by the ovary before mating is concerned in the abrupt change from epithelial to stromal cell division that occurs between days 3 and 4 of pregnancy, and is of importance in the sensitization of the uterus for implantation.