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Biomedical subjects

D T Baird

Publications and source records attributed to D T Baird.

At least 289 records · Page 16Linked to original sources

Prostaglandin synthesis in the endometrium of women with ovular dysfunctional uterine bleeding.

The endogenous concentrations of prostaglandins F2 alpha (PGF 2 alpha) and E (PGE) were measured during the luteal phase of the menstrual cycle in the endometrium from 14 women with unexplained menorrhagia (measured menstrual blood loss in excess of 50 ml) and 15 women with normal menses (blood loss 50 ml or less). Although there was no significant difference in the PGF 2 alpha/PGE ratio between the two groups, this ratio was significantly lower in the endometrium from eight of the women whose blood loss exceeded 90 ml (p less than 0.05). There was a significant inverse correlation between the PGF 2 alpha/PGE ratio and blood loss (r = 0.36, p less than 0.025). The synthetic capacity of the endometrium was assessed by incubation of the tissue with 14C arachidonic acid. Endometria from nine women with unexplained menorrhagia synthesized more PGE2 than PGF 2 alpha, whereas the converse was true with 11 control endometria. Consequently the PGF2 alpha/PGE2 ratio was significantly reduced in the former group (p less than 0.025). Oestradiol-17 beta (200 microM) and to a greater extent 2 hydroxy oestradiol (200 microM) increased the total prostaglandin synthesis by the endometria, but did not significantly alter the PGF2 alpha/PGE2 ratio. These results suggest that excessive blood loss may be associated with a shift in the endometrial conversion of prostaglandin endoperoxide from PGF2 alpha to PGE2.

Adolescent↗

Persistence of symptoms of premenstrual tension in hysterectomized women.

Daily symptom ratings were recorded in seven women with premenstrual tension syndrome for one month before and for up to two months after hysterectomy. Ovarian activity was monitored after operation by twice weekly measurements of total oestrogen and pregnanediol in 12-hour urine samples. Cyclical changes in mood persisted following hysterectomy with the greatest mental and physical symptoms occurring during the late luteal phase of the cycle. In contrast there was a marked decrease in activity and vigour ratings during the late luteal phase of the cycle and during menstruation. There was a small but significant improvement in symptoms in most women following hysterectomy. These results demonstrate that neither the presence of the uterus nor the occurrence of menstruation are necessary for the manifestation of the premenstrual tension syndrome and support the view that it has a hormonal basis.

Adult↗

Ovarian function in the ewe after active immunization against testosterone.

The secretion rates of testosterone measured during the last half of the oestrous cycle in 2 Merino crossbred ewes with utero-ovarian autotransplants were 1.95 +/- 0.34 ng/min and 2.48 +/- 0.63 ng/min. The secretion rate of testosterone was not correlated with the secretion rate of oestradiol or androstenedione in either ewe. Welsh Mountain ewes were actively immunized against testosterone-3-(O-carboxymethyl)-oxime-bovine serum albumin (testosterone-3-BSA) or BSA alone (controls). Immunization against testosterone-3-BSA (5 ewes) resulted in anovulation (2 ewes) and the disruption of oestrous cycles and irregular ovulations (2 ewes). The ovaries showed morphological and endocrinological evidence of over-stimulation. Numerous large non-atretic follicles were present and in those ewes still ovulating the numbers of corpora lutea (ovulation rate) were increased. The concentrations of androstenedione and of oestradiol in the ovarian venous plasma were also markedly increased when compared to those in control ewes. The plasma binding capacity for steroids and the jugular venous concentrations of steroids were higher in immunized ewes. The binding capacity of follicular fluid for testosterone was similar to that of jugular venous plasma from the same ewe. These results show that immunization against testosterone-3-BSA leads to a disruption of ovarian cycles and ovarian over-stimulation.

Androstenedione↗

Increased testicular growth of Tasmanian Merino ram lambs treated with antisera to oestrogens.

Passive immunization against oestrone and oestradiol increased the rate of testicular growth (P less than 0.01) without a statistically significant change in the concentrations of LH and FSH at the time of measurement. Although the concentration of testosterone was higher in the group with the largest testes, the difference was not statistically significant. Within groups, the concentration of FSH was correlated with the oestrone antibody titre (r = 0.5), suggesting that oestrone may have a particular role to play in the feedback control of FSH release in the ram; in addition, the concentration of testosterone was correlated with that of LH (r = 0.65). The data indicate a role of oestrogens in the control of testicular growth and are compatible with earlier reports that the testes of Merino lambs grow more quickly when gonadal feedback is reduced.

Animals↗

Gonadotrophic control of follicular development and function during the oestrous cycle of the ewe.

In the adult non-pregnant ewe the secretion of FSH is sufficient to ensure a continuous growth and development of antral follicles to 3-5 mm size at all times. Further development and increased secretion of oestradiol through the final 72 h to ovulation depends on adequate stimulation by LH. During anoestrus and the luteal phase of the cycle LH pulses occur too infrequently to stimulate sufficient oestradiol to evoke an LH surge. Moreover, during the luteal phase progesterone secreted by the corpus luteum not only reduces the frequency of LH pulses but also inhibits the ability of oestrogen to evoke an LH surge. At the time of luteal regression the frequency of LH pulses increases to at least one per hour due to the fall in progesterone secretion. This change in pulse frequency of LH is associated with a decrease in the secretion of FSH, probably because of a direct inhibitory action of oestrogen on the anterior pituitary gland. The dominant follicle is probably relatively independent of circulating levels of FSH due to the high concentration of oestradiol and FSH within the microenvironment of the follicular cavity. Once the oestrogen secretion achieves a certain level a preovulatory surge of LH (and FSH) occurs. Increased sensitivity of the anterior pituitary to LH-RH and increased secretion of LH-RH from the hypothalamus both play a part in producing the LH surge. The rise in prolactin at this time probably reflects a decrease in hypothalamic dopamine turnover which is necessary for maximum release of LH-RH. The preovulatory LH surge initially stimulates and then totally inhibits further secretion of oestrogen and androgen from the ovulatory follicle. This suppression of steroid secretion is accompanied by a second peak of FSH at about the time of ovulation. The function of this second peak of FSH remains unknown although it may be responsible for the development of the large antral follicles which occur on Days 3 and 4. It is probably more important in those mammals like the rat and hamster which only form a functional corpus luteum if pregnancy occurs and in which oestrogen is necessary for implantation.

Androgens↗

The use of 16-16 dimethyl trans delta 2 PGE1 methyl ester (ONO 802) vaginal suppositories for the termination of early pregnancy. A comparative study.

Vaginal suppositories containing the 16-16 dimethyl trans delta 2 PGE1 methyl ester (ONO 802) were used for the induction of abortion in early pregnancy, and this non-surgical technique was compared with suction termination performed under local anaesthesia or general anaesthesia. Ninety patients were recruited to the study and divided equally between the three groups. Complete abortion was induced in 87 per cent of the patients treated with ONO 802 suppositories, which compared favourably with 87 and 100 per cent for the patients who had suction terminations under local anaesthesia and general anaesthesia respectively. The vaginal suppositories induced uterine bleeding in all patients and the mean time of onset of lower abdominal pain was 2 hours 55 minutes. The average numbers of episodes of vomiting and diarrhoea for patients given ONO 802 suppositories were 0.9 and 0.7 respectively. Menstrual blood loss was measured objectively in all groups and no significant differences between the three methods could be found. In selected cases, ONO 802 vaginal suppositories would seem to be safe and reasonably effective for the termination of early pregnancy.

16,16-Dimethylprostaglandin E2↗

The effect of 17 beta-estradiol and progesterone on prostaglandin production by human endometrium maintained in organ culture.

Endometrium collected from 18 normal women at various stages of the menstrual cycle was maintained in organ culture for periods of 6 days. Both prostaglandin F2 alpha (PGF2 alpha) and PGE were detected in medium from late proliferative (days 10-14; n = 13) and late secretory (days 20-26; n = 5) endometria cultured in the absence of exogenous steroids. During the first 48 h in culture, the output of PGF2 alpha by secretory endometrium was significantly greater than that of proliferative tissue. The addition of 17 beta-estradiol to the culture medium at doses ranging from 1.0-100.0 ng/ml induced a significant increase in the output of PGF2 alpha by secretory but not proliferative endometria. The addition of progesterone at doses ranging from 5.0-500.0 ng/ml significantly reduced the output of PGF2 alpha and PGE by both proliferative and secretory endometria and prevented the 17 beta-estradiol-stimulated increase in PGF2 alpha output by secretory tissue.

Cell Division↗

Ovarian morphology and the concentration of steroids during the oestrus cycle of sheep actively immunized against androstenedione.

Ewes were immunized against androstenedione-11 alpha-hemisuccinyl-bovine serum albumin (androstenedione-11-BSA) or BSA alone (controls). The ovaries were examined macroscopically and ovarian venous blood was collected at laparotomy by in-situ cannulation of the ovarian vein on Day 10 of the oestrous cycle, or by needle puncture of the ovarian vein 36 h after prostaglandin treatment. Follicular fluid was also collected from follicles greater than 5 mm diameter in some ewes. Ovaries and adrenal glands were collected and examined histologically. Oestrone, oestradiol-17 beta, androstenedione, testosterone and progesterone were measured by radioimmunoassays. Immunization against androstenedione-11-BSA was followed by an increase in the number of surface follicles greater than 3 mm in diameter and in ovulation rate. These changes were accompanied by an increased production of androgens (especially androstenedione) and of oestrogens during the preovulatory period. There were no observed changes in the adrenal cortex or pituitary glands, but the ovaries were heavier in immunized ewes and luteinized follicles were present in the ovaries of 1 of 4 immunized ewes. These results show that immunization against androstenedione-11-BSA leads to increased ovulation rate and suggest two possible mechanisms: (1) interference with the negative feedback effects of oestradiol-17 beta and/or (2) a reduction in the incidence of follicular atresia.

Androstenedione↗

Suppression of concentration of endometrial prostaglandin in early intra-uterine and ectopic pregnancy in women.

Concentrations of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E (PGE) were measured in endometrium from 18 women with ectopic pregnancies. In the nine pregnancies not associated with vaginal bleeding or an intra-uterine contraceptive device (IUCD; intact ectopics), concentrations of PGF2 alpha (12.8 +/- 7.4 (S.E.M.) ng/g) and PGE (4.7 +/- 3.0 ng/g) were similar to those in decidua from nine intra-uterine pregnancies of comparable gestational age (14.4 +/- 4.4 and 8.2 +/- 2.2 ng/g respectively). In both ectopic and intra-uterine pregnancies concentrations of prostaglandins were significantly lower than those found in endometrium throughout the normal menstrual cycle (P < 0.01). In nine ectopic pregnancies with associated vaginal bleeding and/or an IUCD, concentrations of PGF2 alpha and PGE were significantly higher than in the intact group (P < 0.05), although the concentration of PGF2 alpha remained significantly lower than levels in normal secretory endometrium (P < 0.05). These results suggested that suppression of endometrial synsthesis of prostaglandin during early pregnancy may be mediated systemically rather than through a local action of the conceptus.

Chorionic Gonadotropin↗

Changes in the binding of human chorionic gonadotrophin/luteinizing hormone, follicle-stimulating hormone and prolactin to human corpora lutea during the menstrual cycle and pregnancy.

The changes in the binding of human chorionic gonadotrophin/luteinizing hormone (HCG/LH), follicle-stimulating hormone (FSH) and prolactin to 44 corpora lutea have been assessed during the luteal phase of the human menstrual cycle and early pregnancy. All corpora lutea bound HCG but out of 32 only ten bound FSH and only seven bound prolactin specifically. While binding of HCG increased to maximal levels in the mid-luteal phase, binding of FSH and prolactin was most often found in the early luteal phase. Maximum binding of HCG was associated with maximum serum levels of progesterone. Luteal regression was associated with a decrease in the binding of HCG but a causal relationship could not be established. Very low binding of HCG was found to corpora lutea of pregnancy. These results show that (1) the changes in binding of HCG during the luteal phase of the human menstrual cycle are similar to those in other species and (2) there are specific binding sites for prolactin and FSH in the human corpus luteum.

Chorionic Gonadotropin↗

Failure of estrogen-induced discharge of luteinizing hormone in lactating women.

Pituitary-ovarian relationships were studied in seven lactating women by measuring the basal plasma concentrations of pituitary and ovarian hormones and their responses to an estrogen provocation test at 7, 30, and 100 days after delivery. The results were compared to a similar group of seven women who did not breast feed. The first ovulation occurred in five of the nonlactating women beteen 43-87 days after delivery, as judged by the urinary excretion of total estrogen and pregnanediol. In all lactating women, ovarian cyclicity was suppressed for at least 150 days after delivery or until weaning. The basal concentration of PRL in lactating women was significantly higher than in the nonlactating women at all three times measured. At 30 and 100 days, the concentration of estradiol was significantly lower in the lactating women, although the basal concentrations of FSH were similar in the two groups. After an injection of 1 mg estradiol benzoate, the concentrations of FSH and LH in plasma were suppressed to a greater extent in lactating than in nonlactating women. In addition, fewer of the lactating group (one of seven and none of seven at 30 and 100 days, respectively) than the nonlactating group (two of seven and five of seven) subsequently showed a rise in the concentration of LH 58--96 h after the estrogen injection (positive feedback). These results suggest that during lactation the hypothalamic-pituitary system is more sensitive to the negative feedback and relatively insensitive to the positive feedback of estrogen.

Adult↗

Impaired estrogen-induced luteinizing hormone release in young women with anovulatory dysfunctional uterine bleeding.

Spontaneous ovarian activity, as reflected by the urinary excretion of total estrogen and pregnanediol measured serially (thrice weekly) over a period of 3-4 months, was studied in nine young women (15-27 yr old) with a history of dysfunctional uterine bleeding of at least 2-yr duration. Results were compared to those obtained in sex regularly menstruating women, aged 23-45 yr. All control women had ovulatory cycles, but seven of the nine patients with DUB failed to ovulate during at least three consecutive cycles. The profiles of urinary total estrogen excretion in these seven subjects were consistent with regular follicular development, but the follicular phase was prolonged and the amount of estrogen excretion increased, as compared to controls. In four of these seven patients, the endometrium had previously shown cystic glandular hyperplasia. Although the release of LH and FSH after injection of 50 micrograms synthetic LRH was normal, the surge of LH induced in response to exogenous estrogen (200 micrograms ethinylestradiol/day for 3 days) was significantly (P less than 0.005) lower in the patients (16.2 +/- 3.7 mU/ml) than that of control women )35.0 +/- 5.5 mU/ml). It is concluded that the failure to ovulate in young women with anovulatory dysfunctional uterine bleeding is due to inadequate release of LH in response to estrogen. The results support the hypothesis that the basic defect in these women may be a decrease of hypothalamic sensitivity to positive feedback.

Adolescent↗

Relationship between follicle-stimulating hormone, androstenedione and oestradiol in human follicular fluid.

The concentrations of FSH, oestradiol and androstenedione in the follicular fluid of normal and cystic human follicles were measured at different stages of the menstrual cycle. In addition, the number of granulosa cells in the follicles was determined. In follicles in which FSH was detectable, the concentration of oestradiol was greater than that of androstenedione, irrespective of the stage of the cycle. In contrast, in those follicles in which FSH was undetectable and in all cystic follicles irrespective of the level of FSH, the concentration of androstenedione was greater than that of oestradiol. In follicles containing FSH there was a highly significant linear correlation between the number of granulosa cells and the concentration of follicular oestradiol (P less than 0.001). It is suggested that in human ovaries up to 90% of the oestradiol in follicular fluid may originate from the granulosa cells.

Adult↗