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Biomedical subjects

N R Adams

Publications and source records attributed to N R Adams.

At least 37 records · Page 2Linked to original sources
PubMed1990

Immunization of ovariectomized ewes against progesterone, oestrogen or cortisol to detect effects of adrenal steroids on reproduction.

Ovariectomized ewes were immunized against cortisol, oestrogen or progesterone to determine whether steroids of non-ovarian origin occur in sufficient amounts to influence the reproductive system. Ewes immunized against oestrogen (oestrone + oestradiol) had smaller uteri (P less than 0.05) and a lower concentration of oestradiol in uterine tissue (P less than 0.05), while the adrenal gland was heavier (P less than 0.05). In the peripheral plasma of immunized ewes, the concentration of FSH, but not LH, was increased (P less than 0.05). Ewes immunized against cortisol also had smaller uteri (P less than 0.05) and heavier adrenal glands (P less than 0.05), but gonadotrophins and the concentration of oestradiol in the uterus were unaffected. Immunization against progesterone, or injection with synthetic glucocorticoids, did not affect any of the characteristics measured. We conclude that the adrenal gland of the ewes produced sufficient oestrogen or aromatizable androgen to have significant effects on the reproductive system. In contrast, adrenal production of progesterone did not produce detectable biological effects. Immunization against cortisol did affect the reproductive system, but the mechanism of this action could not be determined.

Adrenal Glands↗
PubMed1989

LH, FSH and ovulation rate in ewes treated with exogenous oestradiol.

In two experiments, mature Merino ewes were fitted with subcutaneous implants containing oestradiol-17 beta or empty implants (control). Peripheral concentrations of LH and FSH were measured during luteal and follicular phases, which were synchronized by means of intravaginal progestagen-impregnated sponges. The ovulation rates of the ewes were determined by laparoscopy, 1 week after luteolysis. In Exp. 1, small implants (3 mm) decreased the LH pulse frequency before luteolysis. In the ewes with oestradiol implants, the amplitude of the preovulatory surge of LH was reduced and the onsets of the LH and FSH surges were delayed. There was no effect of oestradiol on LH baseline, LH pulse amplitude or in the concentration of FSH during the luteal or follicular phases. In Exp. 2, larger implants (10 mm) were inserted for the luteal, follicular, or luteal + follicular phases. The control ewes had empty implants. In the ewes with oestradiol implants, LH pulse frequencies were decreased during the luteal phase. This decrease persisted throughout the follicular phase, even though the oestradiol implants had been removed. There were no differences in the other measures of LH or FSH in the luteal or follicular phases. Ovulation rates were not affected by oestradiol treatment in either experiment, indicating that the regulation of LH pulse frequency is not a critical factor in the determination of ovulation rate in ewes. This was supported by retrospective analysis of the gonadotrophin profiles of single and twin-ovulating ewes, in which all measures of LH were similar between the two groups. However, twin-bearing ewes had slightly higher circulating concentrations of FSH during the luteal phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of oestradiol implants on the ovulation rate of the ewe.

In a series of 5 experiments, ewes were treated with implants releasing oestradiol-17 beta and the effects on ovulation rate were observed. Large doses of oestradiol-17 beta (greater than 20 micrograms/day) produced anovulation while smaller amounts only reduced the proportion of twin ovulations. Amounts of exogenous oestradiol comparable to ovarian production rate in the luteal phase (less than 1 microgram/day) produced a significant (P less than 0.01) suppression in ovulation rate. Treatment during the follicular phase of the oestrous cycle was most effective, but treatment during the luteal phase alone also appeared to suppress ovulation rate. Furthermore, in 2 of 3 experiments ewes treated with low amounts of oestradiol during the first half of the luteal phase were less likely to have multiple ovulations at the subsequent oestrous period. The results support the hypothesis that oestrogen is involved in the physiological control of ovulation rate in the ewe, but this action is probably not restricted to the assertion of dominance by a maturing follicle during the follicular phase.

Animals↗
PubMed1988

Persistent infertility in ewes after prolonged exposure to oestradiol-17 beta.

Merino ewes were treated with implants which released 300 micrograms oestradiol-17 beta per day or 5 mg progesterone per day, or both, for 9 months (Months 1-9), and after an 11-month intermission were treated again for 6 months (Months 20-26). Ewes were run with rams at Months 16, 28 and 40. Fertility was not affected by the first exposure period, but the second exposure to oestradiol reduced the fertility of ewes at both subsequent mating periods. Affected ewes returned to service more frequently (P less than 0.01) and were less likely to conceive (P less than 0.05). After mating, a normal population of spermatozoa was established in the caudal cervix, but transport through the cervix was impaired in affected ewes and there were fewer spermatozoa (P less than 0.01) in the cranial cervix. In affected ewes, the spinnbarkeit of cervical mucus was reduced (P less than 0.05), and the histological appearance of the cervix changed, looking like that of the uterus. Treatment with progesterone did not affect fertility, cervical mucus or sperm transport, but diminished the histological abnormalities produced by oestradiol (P less than 0.05). These results show that oestradiol-17 beta given after puberty can cause the same kind of permanent sexual transdifferentiation that is produced by the oestrogenic isoflavones in ewes with clover disease. The results suggest that this change may require more than a single exposure to oestrogen.

Animals↗
PubMed1988

Adrenal glands alter the concentration of oestradiol-17 beta and its receptor in the uterus of ovariectomized ewes.

To investigate the effects of adrenal hormones on oestrogen activity in the uterus, ovariectomized ewes were either adrenalectomized, administered glucocorticoid-like preparations (CORT), or remained as controls. The adrenalectomized ewes were maintained with a corticoid-replacement therapy and monitored daily for plasma glucose and Na+/K+ concentrations. Blood samples were collected from all ewes at 15-min intervals for 4 h and assayed for LH and FSH. The adrenalectomized ewes were killed 9 days after adrenalectomy, while the CORT ewes were killed after 3 weeks of drug therapy. The control ewes were killed simultaneously with the CORT ewes. Uterine tissues were homogenized and the numbers of oestradiol receptors and tissue concentrations of oestradiol-17 beta were measured. The adrenalectomized ewes had significantly higher concentrations of cytosolic oestrogen receptors in the uterus than did the control ewes, which had significantly higher concentrations than the CORT ewes (0.95 +/- 0.06, 0.76 +/- 0.02 and 0.60 +/- 0.02 (S.E.M.) mumol/kg protein respectively). The concentrations of oestradiol-17 beta measured in uterine tissues were significantly lower in adrenalectomized and CORT ewes than in control ewes (37.4 +/- 5.5, 61.7 +/- 25.7 and 135.5 +/- 12.8 pmol/kg respectively). There were no significant differences between any groups in the peripheral concentrations of LH or FSH. These results indicate that the adrenal gland affects the concentrations of both oestrogen and its receptor in the uterus of ovariectomized ewes, probably by different mechanisms. These effects are not mediated by gonadotrophins.

Adrenal Glands↗
PubMed1987

Cytosol type II sites in the rat uterus: interaction with an endogenous ligand.

Previous studies from our laboratory demonstrated that normal, but not malignant tissues, contain a ligand which competes for [3H]estradiol binding to nuclear type II sites in the rat uterus. Since elevated nuclear levels of type II sites are correlated with estrogen stimulation of uterine growth and DNA synthesis, we believe this ligand may regulate cell growth. The present studies show that the ligand for nuclear type II sites also interacts with type II sites in uterine cytosol. This was demonstrated by dilution experiments which show that greater quantities of type II sites are measured in dilute (10 mg/ml) than in concentrated (40 mg/ml) uterine cytosol. Furthermore, stripping of uterine cytosol with 1% dextrancoated charcoal, or pre-binding cytosol type II sites to hydroxylapetite (HAP) prior to binding analysis, removed the ligand from these preparations such that high levels of type II sites were measured. Following charcoal stripping, cytosol type II sites demonstrated good specificity for estrogenic hormones but not progesterone, corticosterone, or the triphenylethylene anti-estrogen, nafoxidine. Since the level of type II sites in the cytosol always preceded and exceeded the level of this site measured in uterine nuclei at all times following estrogen treatment (0-96 h), we believe cytosol type II sites may function as an type II-ligand binding protein (LBP) which regulates the availability of the ligand for interaction with nuclear type II sites. This is consistent with our observation that type II sites are not depleted from uterine cytosol by estrogen treatment and nuclear type II sites are very tightly associated with the nuclear matrix.

Animals↗
PubMed1986

Measurement of estrogen receptors in the ovariectomized ewe is affected by body condition and secondary binding sites.

Two studies were carried out to examine possible causes of the variability that occurs in studies on estrogen receptors in sheep. In the first study, the concentration of estrogen receptors in the uterus of a group of 16 ovariectomized ewes was inversely related to their live weight (r = -0.52, p less than 0.05). A second study examined 8 ovariectomized controls and 7 ewes that were permanently infertile after prolonged exposure to estrogenic clover pasture. The concentration of estrogen receptors in the pituitary of these ewes was inversely related to a measure of body fatness (r = -0.67, p less than 0.05), and there were no differences between control and clover-affected ewes. In addition to the classical estrogen receptor with a dissociation constant of 0.03 X 10(-9) mole/L, there were secondary binding sites with dissociation constants of about 0.9 X 10(-9) mole/L in the pituitary. The amount of this binding varied among sheep and appeared to increase as the cytosol was diluted. It is suggested that a failure to distinguish the presence of these sites may have led to apparent differences between experimental groups in the amount of affinity of receptors in previous studies. The effect of body condition on the number of cytosolic receptors may also have confounded previous studies.

Adipose Tissue↗
PubMed1986

The effect of zeranol and testosterone on Merino wethers exposed to highly oestrogenic subterranean clover pasture.

Groups of Merino wethers treated with 2 doses of zeranol (6 mg and 12 mg), or testosterone cyclopentyl propionate (150 mg) and untreated controls were grazed at 2 sites, one an oestrogenic subterranean clover (Trifolium subterraneum) pasture and the other a low oestrogen medic (Medicago truncatula) pasture. The influence of oestrogenic subterranean clover on these treatments was assessed by measuring changes in teat length, bulbourethral gland weight and pathology, bodyweight, carcase weight, dressing percentage and greasy and clean fleece weights. Teat lengths were increased by all treatments except 6 mg of zeranol where increases were not significant, and although increased by exposure to oestrogenic pasture this effect were not additive. Bulbourethral gland weights were increased by both of the zeranol treatments and by oestrogenic pasture, and these effects appeared to be additive. Differences observed histologically indicated that testosterone protected whereas zeranol exacerbated the influence of oestrogen. The bodyweights of all treated groups were heavier than the controls, but carcase weights were not significantly different. However an effect was seen in the group given the 6 mg dose of zeranol on the low oestrogen site, where the dressing percentage was significantly lower than in the control and testosterone treated groups. Differences in greasy and clean fleece weights were not significant except that the washing yield of the testosterone-treated group was significantly lower at the low oestrogen site.

Animal Feed↗
PubMed1986

Measurement of histological changes in the cervix of ewes after prolonged exposure to oestrogenic clover or oestradiol-17 beta.

Morphometric methods were used to measure abnormalities in histological architecture of the endocervix in ewes with infertility after prolonged exposure to oestrogenic clover pastures. Similar measurements were made on the cervix of ewes exposed to oestradiol-17 beta for 6 months. In both cases the changes in histological appearance were essentially similar, and were most easily measured by counting the number of cervical crypts. Ewes treated with either phyto-oestrogens or oestradiol also had significantly wider cervical folds, greater areas of lamina propria, and more cervical glands. The results provide a basis for measuring the severity of permanent oestrogenic change in different flocks or after different experimental treatments.

Animal Feed↗
PubMed1986

Changed control of cervical secretion from infertile ewes previously exposed to oestrogenic clover pasture.

The amount of cervical mucus recovered from control ovariectomized ewes increased with increasing doses of oestradiol benzoate (OB), while the maximum Spinnbarkeit of mucus occurred at an intermediate dose of OB. Neither the amount nor the Spinnbarkeit of mucus varied with the dose of OB in ewes with permanent infertility caused by grazing oestrogenic pasture (clover-affected ewes). Furthermore, the increase in Spinnbarkeit of cervical mucus seen in normal ewes treated over a 3-day period with OB or with implants containing oestradiol did not occur in affected ewes. In control ewes treated repeatedly with OB, production of mucus declined within 5 days, but no change in secretion was detectable in clover-affected ewes. Therefore, neither the amount nor the duration of oestrogenic stimulation affected the cervical mucus in ewes with clover disease. Affected ewes produced more mucus than did controls in the absence of oestrogenic stimulation. It is concluded that the relatively normal volume of mucus in affected ewes treated with OB results largely from autonomous production. The Spinnbarkeit does not increase in these ewes because the ability of the cervix to respond to oestrogen is impaired.

Animals↗
PubMed1986

Morphogenic change in the cervix of the ewe after prolonged exposure to oestradiol-17 beta.

This study examined the effects of prolonged exposure to oestradiol-17 beta on the morphology of the cervix of the ewe. Merino ewe lambs were implanted subcutaneously with 3 Silastic capsules which released a total of approximately 300 micrograms oestradiol-17 beta per day. After exposure for 200 days the uterus was more markedly bicornuate, and the cervix was broader and softer, than in controls. The cervical folds were shorter and contained many stromal cells. The amount of lamina propria under the folds was increased and altered so that it contained tubular glands and more stromal cells. The endocervix thus came to resemble endometrium. This appearance developed within 80 days of exposure, and remained for at least 170 days after implant removal. In a second experiment, mature multiparous Merino ewes were ovariectomized and implanted with 1, 2 or 4 similar oestradiol capsules for 140 days. Similar features developed in these ewes, and the degree of change was almost as great with 1 implant as with 4. Changes of a similar nature can be produced in other species by oestrogen given during organogenesis but not during adult life. The changes indicate that the ewe has an ability to display a degree of morphogenic response to oestradiol during adult life.

Animals↗
PubMed1986

Apparently normal oestrogen receptor system in ovariectomized ewes with impaired response to oestrogen after prolonged grazing on oestrogenic pasture.

Functional abnormalities have been observed previously in the oestrogen-responsive tissues of ovariectomized ewes with permanent infertility resulting from prolonged exposure to oestrogenic pastures. In the present study, such ewes had higher rates of protein and glycoprotein synthesis in the cervix and uterus than control ewes, but the number of oestradiol-17 beta receptors in the nucleus was similar in each group. After treatment with oestradiol-17 beta, the increase in synthesis of protein and glycoprotein in the uterus and cervix was less in clover-affected ewes, but the amount of oestradiol-17 beta-receptor complex in the nucleus of uterine cells 6 h after ewes were injected with oestradiol-17 beta was similar in clover-affected and control ewes. The rate of replenishment of oestradiol-17 beta receptors in the cytoplasm at 24 and 48 h after oestradiol-17 beta injection was also similar in both groups. The abnormal function seen in the genital tract of clover-affected ewes could not, therefore, be shown to depend on changes in oestradiol-17 beta receptors.

Animals↗
PubMed1983

Effects of oestradiol on plasma concentrations of luteinizing hormone in ovariectomized ewes with clover disease.

The effects of oestradiol on plasma luteinizing hormone (LH) concentrations were examined in 15 ovariectomized control ewes and 15 similar ewes with permanent infertility after prolonged grazing on oestrogenic clover pasture ('clover disease'). Before treatment, the plasma concentrations of LH were similar in the control and affected ewes. After intravenous injection with 40 micrograms oestradiol-17 beta during the anoestrous season, the decline in LH concentration was greater in the clover-affected ewes and the subsequent elevation above original baseline levels was smaller. After intramuscular injection with 15 or 30 micrograms oestradiol benzoate during the normal breeding season, fewer clover-affected ewes showed a surge of LH, and the response was both reduced and retarded. This difference between the two groups has not been observed in studies on intact ewes, and it is suggested that in intact ewes the difference is masked by a greater tonic LH activity in affected ewes. The results of the present study are consistent with the hypothesis that prolonged exposure to oestrogenic pasture has a differentiating, or 'androgenizing' effect on the adult ewe.

Animals↗
PubMed1983

Sexual behaviour of ewes with clover disease treated repeatedly with oestradiol benzoate or testosterone propionate after ovariectomy.

Ovariectomized ewes, 14 with permanent clover disease infertility (affected ewes) and 14 controls, were injected daily with 40 micrograms oestradiol benzoate for 12 days, and run with 2 rams fitted with marking crayons. The control ewes were mated sooner (P less than 0.05) but both groups became refractory at a similar rate. In a second experiment, 20 similar affected ewes and 19 controls were injected daily with 5 mg testosterone propionate for 31 days and observed daily for 50 min with rams. Affected ewes again were slower to show female behaviour (P less than 0.05) but faster (P less than 0.05) to show aggression against the rams and other ewes. Over the 31 days, the incidence of female sexual behaviour declined at a similar rate in affected and control ewes. When examined in individual pen tests with oestrous ewes on Day 28, affected ewes showed more male-like courting behaviour than did controls (P less than 0.05). The changes in behaviour are too slight to account for the infertility but they do support the hypothesis that phyto-oestrogens can act on the ewe by some of the pathways of sexual differentiation, even after puberty.

Animals↗
PubMed1982

Proportions of nucleic acids in the uteri of ewes with clover disease and the effect of oestrogen after ovariectomy.

In entire ewes, the ratio of RNA to DNA in the uterus was higher at oestrus than at dioestrus but did not differ between control and clover-affected ewes at either stage of the oestrous cycle. After ovariectomy the ratio of RNA to DNA in the uteri decreased in both control and clover-affected ewes, but the decrease was greater in the control ewes (P less than 0.01). Subsequently when ewes received a single injection of oestradiol-17 beta, a similar rise in uterine RNA/DNA ratio occurred in the two groups. However, following injection of the ewes with oestradiol-17 beta for 3 days, the ratio of uterine RNA to DNA was higher in control than in clover-affected ewes (P less than 0.05). Thus, the uteri from clover-affected ewes undergo less regression after ovariectomy and yet show less response to repeated oestrogenic stimulation that do that of control ewes. This pattern of response is consistent with the hypothesis that the permanent changes caused by phyto-oestrogens in ewes are analogous to the differentiation which normally occurs during organogenesis.

Animals↗
PubMed1981

Hypothalamic-pituitary function in normal ewes and ewes which grazed oestrogenic subterranean clover for several years.

Plasma luteinizing hormone (LH) concentrations were measure in normal Merino ewes and in Merino ewes with lowered fertility which had resulted from prolonged grazing of Trifolium subterraneum L. cv. Dinninup. During the anoestrous season, LH was measured at frequent intervals before and following administration of oestradiol-17 beta or gonadotropin releasing hormone (GnRH), and around the time of spontaneous oestrus. All ewes responded to GnRH treatment and there were no differences between the two groups in terms of the amount of LH released or the time to reach maximal plasma hormone concentration. Comparable proportions of ewes from both groups responded to oestradiol-17 beta treatment with LH levels showing initially a negative feedback response (i.e. suppression to approximately 80% of pretreatment levels) followed by positive feedback response. During the positive feedback phase, the quantity of LH which was released was comparable in both groups; however, the time interval over which this hormone was secreted was significantly shorter for clover-infertile ewes (P less than 0.05). During the anoestrous season the mean LH level was lower in normal ewes than in clover-infertile ewes [0.45 +/- 0.41 (n = 32) versus 0.82 +/- 0.73 (n = 48 ng/ml, P less than 0.01]. In the oestrous season the mean LH level for normal ewes rose to 1.23 +/- 0.65 ng/ml (n = 76) but there was no change for the clover-infertile ewes (0.77 +/- 0.59 ng/ml, n = 73). These experiments indicate that in the clover-infertile ewe LH concentration remains static throughout the breeding and non-breeding seasons but the results suggest that this altered endocrine status in not due to any differing level of sensitivity to negative feedback effects of oestradiol-17 beta as compared with normal ewes.

Animal Feed↗
PubMed1981

Oestrogen receptors and metabolic activity in the genital tract after ovariectomy of ewes with permanent infertility caused by exposure to phytooestrogens.

Characteristics of the uterus anc cervix after ovariectomy of ewes with permanent phytooestrogen infertility (PPI) were compared with controls. Ewes with PPI had more oestrogen-binding sites in the cervix, but not in the uterus. There was no difference between the two groups of ewes in the binding affinity constant of receptors from the uterus or cervix. There were more keratinized cells in the vaginal epithelium of ewes with PPI, and the rates of protein and glycoprotein synthesis in the uterus and cervix were higher in ewes with PPI. These results offer further evidence that PPI in adult ewes is similar to the "persistent oestrus' syndrome in rodents oestrogenized neonatally.

Animals↗