The effect of exogenous oxytocin on luteal function in mares

Daily injections of 150 units oxytocin administered to 6 mares on Days 4, 5, 6, 7 and 8 after ovulation (Day 0 = ovulation) failed to induced luteolysis as indicated by the maintenance of normal plasma progestagen concentrations and the occurrence of normal ovulatory intervals. Three additional mares were given oestrogen injections 24 h before an injection of oxytocin on Day 7 after ovulation, but this treatment also failed to induce luteolysis since plasma progestagen concentrations were maintained in all three mares. Two mares exhibited normal ovulatory intervals, while the third developed a corpus luteum which persisted for 46 days.     

Effects of the presence of a dominant follicle and exogenous oestradiol on the duration of the luteal phase of the bovine oestrous cycle.

The presence of a developing dominant follicle may be a factor in the control of the luteolytic cascade mechanism and the number of follicular waves during the bovine oestrous cycle. In this study, ovaries of all animals were examined once a day by transrectal ultrasonography. It was expected that heifers (n = 18) would have two follicular waves if the second wave occurred later than day 10 after oestrus (Expt 1) and that cows (n = 14) would have three waves if the second wave occurred on or before day 10 (Expt 2). The objective of Expt 1 was to determine if absence of a large follicle late in the luteal phase delays luteal regression in heifers that are expected to have two follicular waves. Nine heifers were injected i.v. with 10 ml charcoal-treated bovine follicular fluid three times a day for 4 days, starting on the day after initiation of the second follicular wave, to delay growth of the second wave dominant follicle. Nine heifers were injected with 0.9% NaCl as controls. The duration of the luteal phase (calculated as the number of days that serum progesterone was > 0.5 ng ml-1) was greater (P < 0.01) in the follicular fluid-treated group compared with the controls (18.7 versus 14.1 days). FSH and follicular growth were suppressed during the period of injection of follicular fluid (P < 0.01 and 0.03, respectively). The objective of Expt 2 was to determine the effect of increased oestradiol on the duration of the luteal phase in cows that were expected to have three follicular waves. Seven cows were injected i.m. three times a day for 4 days with 1 ml oestradiol (100 micrograms ml-1 in corn oil) and seven cows were similarly injected three times a day with 1 ml 0.9% NaCl (control) starting the day after cessation of growth of the second wave dominant follicle. Luteal phase duration was shorter in oestradiol-treated animals than in the controls (14.0 versus 19.0 days; P < 0.04). Serum oestradiol concentrations were higher in the oestradiol-treated group during the period of injection (P < 0.01). In summary, luteolysis was delayed when follicular growth was suppressed with follicular fluid (Expt 1). Exogenous oestradiol administration during the development of uterine oestradiol responsiveness initiated luteolysis earlier compared with control animals (Expt 2).     

Independent effects of endogenous and exogenous attention in touch

Abstract

Endogenous and exogenous attention in touch have typically been investigated separately. Here we use a double-cueing paradigm manipulating both types of orienting in each trial. Bilateral endogenous cues induced long-lasting facilitation of endogenous attention up to 2?s. However, the exogenous cue only elicited an effect at short intervals. Our results favour a supramodal account of attention and this study provides new insight into how endogenous and exogenous attention operates in the tactile modality.     

The relationship between factors affecting endogenous oestradiol levels in postmenopausal women and breast cancer

Breast cancer accounts for 1 in 4 of all female cancers worldwide; approaching 13,000 women dying per year in the UK alone. Seventy five per cent of all diagnosed breast cancers are oestrogen receptor (ER) positive. Ovarian synthesis of oestrogens ceases at menopause and as breast cancer is more prevalent in postmenopausal women the non-ovarian sources of oestrogen are important in disease progression. There is now considerable evidence that associates increased breast cancer risk with prolonged exposure to oestrogens hence greater attention is now being given to determining whether the measurement of plasma oestrogen may assist in identifying chemoprevention target groups. Studies suggest that in most postmenopausal patients the intra-tumoural concentrations of oestrogens are up to 20-fold higher than those present in the plasma however, while the extent of biosynthesis of oestrogens within breast tissue is a major determinant of local exposure, plasma levels are a useful indicator of overall metabolism in peripheral tissues. As such it is important to understand factors that influence these measurements. This review summarises the impact of lifestyle such as body mass index, together with the role of genetic polymorphisms placed within the context of designing future epidemiological studies and breast cancer risk algorithms.     

Progesterone production by dispersed luteal cells of non-pregnant cows: effects of oxytocin and oestradiol

The effects of oxytocin and oestradiol on progesterone production by dispersed luteal cells of non-pregnant cows were studied. In acute incubation (3 h), oxytocin, at a concentration of 800 mIU/ml, significantly inhibited the production of progesterone induced by HCG (10 IU/ml). Suppression of basal progesterone production was evident in some corpora lutea. Lower oxytocin concentrations (4 and 40 mIU/ml) had no effect. At a concentration of 400 mIU/ml, oxytocin may be inhibitory to basal and HCG-induced progesterone production. Oestradiol (1 μkg/ml) had no effect on basal progesterone production but may suppress the production of progesterone induced by HCG. However, incubation with oxytocin (400 mIU/ml) plus oestradiol (1 μg/ml) resulted in a significant inhibition of HCG-induced progesterone production. These data provide evidence for an inhibitory effect of oxytocin on the corpus luteum of non-pregnant cows. Oestradiol may interact with oxytocin to inhibit the bovine corpus luteum function.     

Deleterious effects of endogenous and exogenous testosterone on mesenchymal stem cell VEGF production

Modulating the paracrine effects of bone marrow mesenchymal stem cells (BMSCs) may be important for the treatment of ischemic myocardial tissue. In this regard, endogenous estrogen may enhance BMSC vascular endothelial growth factor (VEGF) production. However, little information exists regarding the effect of testosterone on stem cell function. We hypothesized that 1) endogenous or exogenous estrogen will enhance stem cell production of VEGF and 2) endogenous or exogenous testosterone will inhibit BMSC VEGF production. BMSCs were collected from adult male, female, castrated male, and ovariectomized female rats. One hundred thousand cells were incubated with testosterone (1, 10, or 100 nM) or estrogen (0.15, 1.5, or 15 nM) for 48 h. Cell supernatants were collected, and VEGF was measured by ELISA. BMSCs harvested from castrated males, normal females, and ovariectomized females produced more VEGF compared with normal males. Castration was associated with the highest level (1,018 +/- 98.26 pg/ml) of VEGF production by BMSCs, which was significantly more than that produced by BMSCs harvested from normal male and normal female animals. Exogenous testosterone significantly reduced VEGF production in BMSCs harvested from ovariectomized females in a dose-dependent manner. Exogenous estrogen did not alter BMSC VEGF production. These findings suggest that testosterone may work on BMSCs to decrease protective growth factor production and that effective removal of testosterone's deleterious effects via castration may prove to be beneficial in terms of protective factor production. By manipulating the mechanisms that BMSCs use to produce growth factors, we may be able to engineer stem cells to produce maximum growth factors during therapeutic use.     

The effect of human chorionic gonadotrophin and exogenous progesterone on luteal function during early pregnancy in pony mares

Previous reports have indicated that repeated administrations of human chorionic gonadotrophin (hCG) to pony mares before day 38 of gestation caused pregnancy failure, but that this could be prevented by the prior or simultaneous administration of progesterone. The present paper describes the circulating progestagen concentrations during these experiments, and shows that pregnancy failure resulted from luteolysis after hCG administration. Most of the mares which received progesterone maintained their pregnancies after hCG injection, but progestagen concentrations fell, suggesting that partial lysis of the corpus luteum occurred. After day 38 of gestation repeated doses of hCG had no effect on plasma progestagen concentrations.     

Effect of A-nor steroids and oestradiol on progesterone production by human luteal cells

Cell suspensions were prepared from human corpora lutea obtained during the mid-luteal phase. Progesterone production was assessed after short-term incubation of luteal cell suspensions. Luteal cells were very sensitive to hCG, the concentration required for 50% maximum response being 0.01 i.u./ml, and the response was 5 times higher than the basal production. Oestradiol (1-100 microM) induced a significant dose-related decrease in both basal and hCG-stimulated progesterone production. The A-nor steroidal compounds anordrin and AF-45 reduced hCG-stimulated progesterone production only at the high concentration of 100 microM. The ED50 values were approximately 3 microM, 75 microM and 100 microM for oestradiol, AF-45 and anordrin respectively. Anordrin showed no significant effects on basal progesterone production. In addition, oestradiol markedly inhibited the activity of 3 beta-hydroxysteroid dehydrogenase in luteal cells, expressed by the conversion of pregnenolone to progesterone, but the inhibitory effects of anordrin and AF-45 were negligible or relatively low. The effects of anordrin and AF-45 were different from those of oestradiol on progesterone production by human luteal cells in vitro, indicating that neither substance is likely to be a useful luteolytic agent in women.     

Prostaglandin regulation of macrophage function: Effect of endogenous and exogenous prostaglandins

The expression of macrophage antitumor activity and the production of prostaglandins (PG) by operationally defined macrophage populations differed under varying culture conditions. Culture conditions that caused increased PGE₂ production by activated macrophages resulted in an inhibition of their tumoricidal activity. In contrast, production of high levels of PGE₂ by resident and elicited macrophages was associated with an increase in antitumor activity. The activation of resident or elicited cells by lipopolysaccharide (LPS) could be blocked by indomethacin. Treatment of these macrophages with PGE₂ alone also resulted in their activation and subsequent tumor cell destruction. Activation of resident and elicited macrophages by LPS appears to be mediated by PGE₂.     

Decreased thermal conductance during the luteal phase of the menstrual cycle in women

To study the influence of the menstrual cycle on whole body thermal balance and on thermoregulatory mechanisms, metabolic heat production (M) was measured by indirect calorimetry and total heat losses (H) were measured by direct calorimetry in nine women during the follicular (F) and the luteal (L) phases of the menstrual cycle. The subjects were studied while exposed for 90 min to neutral environmental conditions (ambient temperature 28 degrees C, relative humidity 40%) in a direct calorimeter. The values of M and H were not modified by the phase of the menstrual cycle. Furthermore, in both phases the subjects were in thermal equilibrium because M was similar to H (69.7 +/- 1.8 and 72.1 +/- 1.8 W in F and 70.4 +/- 1.9 and 71.4 +/- 1.7 W in L phases, respectively). Tympanic temperature (Tty) was 0.24 +/- 0.07 degrees C higher in the L than in the F phase (P less than 0.05), whereas mean skin temperature (Tsk) was unchanged. Calculated skin thermal conductance (Ksk) was lower in the L (17.9 +/- 0.6 W.m-2.degrees C-1) than in the F phase (20.1 +/- 1.1 W.m-2.degrees C-1; P less than 0.05). Calculated skin blood flow (Fsk) was also lower in the L (0.101 +/- 0.008 l.min-1.m-2) than in the F phase (0.131 +/- 0.015 l.min-1.m-2; P less than 0.05). Differences in Tty, Ksk, and Fsk were not correlated with changes in plasma progesterone concentration. It is concluded that, during the L phase, a decreased thermal conductance in women exposed to a neutral environment allows the maintenance of a higher internal temperature.     

The effects of endogenous and exogenous androgens on cardiovascular disease risk factors and progression

Cardiovascular disease incidence rates have long been known to significantly differ between the two sexes. Estrogens alone fail to explain this phenomenon, bringing an increasing amount of attention to the role of androgens. Contrary to what was initially hypothesized, androgens seem to have an overall cardioprotective effect, especially in men. Recent studies and published data continue to support this notion displaying a consistent inverse correlation with atherosclerosis progression and cardiovascular disease both in regressive and prospective study models. Clinical studies have also revealed what seems to be a differential androgenic effect on various cardiovascular risk factors between men and women. Further insight indicates that in order to avoid confusion it may be also preferable to separately examine the effects of endogenous androgen levels from exogenous testosterone administration, as well as discern the differential results of low to normal and supraphysiological administration doses. This review summarizes old and recent data according to the above distinctions, in an attempt to further our understanding of the role of androgens in cardiovascular disease.     

Stimulatory effects of endogenous and exogenous nitric oxide on gastric acid secretion in anesthetized rats

We previously reported the stimulatory effect of endogenous nitric oxide (NO) on gastric acid secretion in the isolated mouse whole stomach and histamine release from gastric histamine-containing cells. In the present study, we investigated the effects of endogenous and exogenous NO on gastric acid secretion in urethane-anesthetized rats. Acid secretion was studied in gastric-cannulated rats stimulated with several secretagogues under urethane anesthesia. The acid secretory response to the muscarinic receptor agonist bethanechol (2 mg/kg, s.c.), the cholecystokinin(2) receptor agonist pentagastrin (20 microg/kg, s.c.) or the centrally acting secretagogue 2-deoxy-D-glucose (200 mg/kg, i.v.) was dose-dependently inhibited by the NO synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 10 or 50 mg/kg, i.v.). This inhibitory effect of L-NNA was reversed by a substrate of NO synthase, L-arginine (200 mg/kg, i.v.), but not by D-arginine. The histamine H(2) receptor antagonist famotidine (1 mg/kg, i.v.) completely inhibited the acid secretory response to bethanechol, pentagastrin or 2-deoxy-D-glucose, showing that all of these secretagogues induced gastric acid secretion mainly through histamine release from gastric enterochromaffin-like cells (ECL cells). On the other hand, histamine (10 mg/kg, s.c.)-induced gastric acid secretion was not inhibited by pretreatment with L-NNA. The NO donor sodium nitroprusside (0.3-3 mg/kg, i.v.) also dose-dependently induced an increase in acid secretion. The sodium nitroprusside-induced gastric acid secretion was significantly inhibited by famotidine or by the soluble guanylate cyclase inhibitor methylene blue (50 mg/kg, i.v.). These results suggest that NO is involved in the gastric acid secretion mediated by histamine release from gastric ECL cells.     

Interactive effects of exogenous and endogenous factors on demographic rates of an African rodent

Exogenous and endogenous environmental factors can have simultaneous additive as well as interacting effects on life‐history traits. Ignoring such interactions can lead to a biased understanding of variability in demographic rates and consequently population dynamics. These interactions have been the focus of decades‐long debates on the mechanisms underlying small mammal population fluctuations. They have often been studied indirectly through seasonal effects, but studies considering them directly and more mechanistically are rare. We investigated the joint effects of exogenous (temperature, food availability) and endogenous (population density) factors on the demographic rates of a group‐living diurnal rodent, the African striped mouse Rhabdomys pumilio using nine‐year mark–recapture data from a population in the Succulent Karoo, South Africa. In general, higher temperatures and lower food availability were associated with higher survival, whereas high population densities were either beneficial or detrimental to survival depending on interacting food availability. High reproductive rates were related to lower temperatures, higher food availability and lower population density, and interactions among environmental factors mediated the strength of these relationships. Our study highlights the complex ways in which different environmental factors can interact to shape demographic rates and emphasizes the importance of explicitly including interactions among exogenous and endogenous factors into studies of population dynamics.     

The infusion of glucose in ewes during the luteal phase increases the number of follicles but reduces oestradiol production and some correlates of metabolic function in the large follicles

Short-term nutritional supplementation stimulates folliculogenesis in ewes probably by insulin-mediated actions of glucose in the follicle. The aim of this study was to determine the effect of glucose on follicle number and granulosa levels of Aromatase P450 and phosphorylated Akt and AMPK. Twelve Ile-de-France ewes were allocated to two groups; one (n=7) infused with saline and the other (n=5) with glucose (10mM/h) for 72h in the luteal phase. At the end of infusion, ovaries were collected and all follicles >1mm in diameter were dissected to recover granulosa cells. Aromatase P450 and phosphorylated Akt and AMPK were analysed by Western blotting of granulosa cell lysates. Blood plasmas collected before and during the infusions were analysed for progesterone, oestradiol, LH, FSH, glucose, insulin and IGF-I. The infusion of glucose significantly increased follicle number but, significantly reduced Aromatase P450 and phosphorylated Akt and AMPK in granulosa cells. The circulating concentration of glucose rose significantly 3h after the start of the glucose infusion and remained elevated until 27h then fell; the circulating concentration of insulin rose significantly by 3h and remained elevated. The circulating concentration of oestradiol fell significantly by 32h and remained low; the circulating concentrations of LH and FSH were unaffected. These data show that short-term infusion of glucose stimulated follicular growth but decreased Aromatase P450 in granulosa cells. The reduced levels of phosphorylated Akt and AMPK suggest that the phosphatidylinositol 3-kinase pathway has been inhibited by high concentrations of glucose. These data also suggest that there may be functional cross-talk between FSH and insulin signalling in granulosa cells.     

The effects of RU486 on the luteal phase of the rhesus monkey

RU486 is a steroid which possesses great affinity for the progesterone (P) receptor, but which has no P activity. It has been shown to be, as a result, a potent P antagonist. In the present study, we investigated the effect of this compound on the luteal phase of the rhesus monkey. The day of ovulation was diagnosed with a +/- 12 h accuracy, using serial laparoscopies and serum estradiol (E2) determinations, in regularly cycling rhesus monkeys. RU486 was administered by gavage (10 mg daily) in different regimens during the luteal phase: Group 1, days 1-5; Group 2, days 5-9; Group 3, days 9-13; and Groups 4, days 9-13, plus hCG (30, 60, 90, 180 and 360 IU i.m. on days 6-10). RU486 induced vaginal bleeding within 24-72 h after the initial administration in Groups 1-3. Animals of Group 4 presented luteal lengths ranging from 9-12 days. Progesterone concentrations at the onset of vaginal bleeding were 2.1 +/- 0.3, 4.9 +/- 0.6, 2.6 +/- 0.4 and 11.2 +/- 1.5 ng/ml (x +/- SEM) for animals of Groups 1-4, respectively. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), E2 and P levels were not altered during treatment. The availability of a compound such as RU486, that consistently induces vaginal bleeding due to its action at the target level (endometrium) without affecting the hormonal events of the menstrual cycle, opens a new approach to post-coital and interceptive contraception.     

The contribution of endogenous and exogenous effects to radiation-induced damage in the bacterial spore

Radical scavengers such as polyethylene glycol 400 and 4000 and bovine albumin have been used to define the contribution of exogenous and endogenous effects to the gamma-radiation-induced damage in aqueous buffered suspensions of Bacillus pumilus spores. The results indicate that this damage in the bacterial spore is predominantly endogenous both in the presence of 1 atmosphere of oxygen, and in anoxia.