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In the normal oestrous cycle of the rat, a fluid accumulates in the uterine lumen during proestrus and oestrus. This fluid has an unusually high K+ concentration (Ringler, 1961). The function of the fluid may be important in capacitation of spermatozoa (Austin, 1951) or in sperm transport.
In the present study, administration of oestradiol (1·0 μg/day for 3 days) to ovariectomized rats resulted in an accumulation of fluid in the uterine lumen similar to that described by Ringler (1961). When the dose of oestradiol was increased to 10 μg/day for 3 days, the volume of fluid which accumulated increased and the concentration of K+ also increased to a maximum of 40–45 mequiv./l. The Na+ concentration decreased concomitantly so that the sum of the concentrations of the two ions remained constant and suggested the presence of an exchange mechanism.
An attempt was made to alter the Na+ and K+ concentrations with
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ABSTRACT
The potency and maximum effect of the calcium entry blocker nifedipine as an inhibitor of uterine contractions in vivo are increased in rats in late pregnant compared with non-pregnant rats. The influence of ovarian steroids produced during pregnancy (oestrogen and progesterone) on the potency and maximum effect of two calcium entry blockers (nifedipine and diltiazem) against uterine contractions during i.v. infusion was therefore investigated in anaesthetized non-pregnant rats. The influence of pregnancy on the relationship between serum concentrations of diltiazem during i.v. infusion and uterine and cardiovascular effects was also investigated.
A twofold increase in the potency of nifedipine as an inhibitor of uterine contractions was observed in rats treated with oestrogen or oestrogen plus progesterone compared with rats treated with corn oil. There was no change in potency in rats receiving progesterone alone. Maximum inhibition of uterine contractions by nifedipine was significantly increased by all three hormone treatments.
A twofold increase in the potency of diltiazem and a significant increase in maximum inhibition of uterine contractions was observed in rats in late pregnancy compared with non-pregnant rats. No increase in potency of diltiazem in reducing blood pressure or heart rate was observed in rats in late pregnancy. No significant difference in potency of diltiazem against uterine contractions was observed in rats treated with oestrogen, progesterone or oestrogen plus progesterone.
In order to determine if the hormone-induced changes in the potency of nifedipine against contractions in vivo were due to a direct effect of the ovarian steroids on voltage-operated calcium channels of the uterus or were mediated by extra-uterine mechanisms, the potency of nifedipine as a relaxant of uterine spasms in vitro was investigated. The potency of nifedipine in the isolated uterus as a relaxant of the spasm induced by KC1 did not differ between rats which received oestrogen, progesterone or oestrogen plus progesterone or corn oil. Additionally, the potency of nifedipine to inhibit oxytocin-driven phasic tension development was not affected by treatment with oestradiol.
These findings suggest that the increase in potency and maximum effect of nifedipine against uterine contractions observed previously in rats in late pregnancy can be ascribed, in part, to the action of the ovarian steroids (oestrogen and progesterone). The increase in potency of diltiazem observed in rats in late pregnancy, however, is due to factors other than oestrogen and progesterone. The lack of effect of hormonal manipulations on the potency of nifedipine on the isolated uterus suggests that the changes in potency in vivo due to oestrogen and progesterone are mediated by extra-uterine mechanisms.
J. Endocr. (1988) 118, 251–258
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SUMMARY
A comparison of oestrogen and neutral 17-oxosteroid excretion in normal Bantu and White subjects shows that the Bantu tends to have a higher total oestrogen excretion, a different oestrogen fractional pattern, and a lower total 17-oxosteroid excretion. In disease there are further differences in oestrogen pattern, the Bantu excreting more oestradiol-17β. 17-Oxosteroids are uniformly decreased and reach very low levels in primary carcinoma of the liver. White cirrhotic patients show an increase in the oestriol fraction. These differences in oestrogenandrogen metabolic balance may be of importance in view of the different disease patterns in the two racial groups.
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ABSTRACT
Bovine FSH (bFSH) was used to immunize BALB/c mice. Spleen cells were fused to the SP 2/0 cell line to produce hybridomas that secreted monoclonal antibodies to bFSH. One of these antibodies (USDA-bFSH-MC28) was extensively characterized and found to be a gamma 1 with kappa light chains, having extremely low cross-reactivity with other bovine pituitary hormones and with ovine and porcine FSH. The dissociation constant as measured by Scatchard analysis was 4·3 nmol/l, and proved to be in a very useful range for affinity chromatography. In an essentially one-step immunoaffinity chromatography procedure, bFSH was easily isolated in a single chromatographic step from crude anterior pituitary homogenate with better yield and with the same purity as classical chromatographic techniques.
J. Endocr. (1987) 115, 283–288
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ABSTRACT
ICI 182,780 is a potent specific pure antioestrogen which may offer advantages in breast cancer treatment compared with partial agonists like tamoxifen. To characterize further the potency and efficacy of ICI 182,780, its effects on the uterus of ovariectomized, oestrogen-treated monkeys (Macaca nemestrina) have been measured using magnetic resonance imaging (MRI). Quantitative MRI allows accurate non-invasive repetitive measurements of endometrial and myometrial volume following hormonal treatments, using each animal as its own control. Single i.m. injections of a long-acting oil-based formulation of ICI 182,780 sustained blockade of oestradiol action on the monkey uterus in a dose-dependent manner for 3–6 weeks. Repeated injections of 4 mg ICI 182,780/kg at 4-weekly intervals provided increasingly effective blockade of uterine proliferation. In a short-acting formulation, ICI 182,780 also completely blocked the trophic action of oestradiol, administered concurrently, in ovariectomized monkeys. Similarly, ICI 182,780 caused involution of the uterus stimulated by prior treatment with oestradiol. The rate and extent of uterine involution in monkeys treated with ICI 182,780 was similar to that seen following oestrogen withdrawal. These studies demonstrate that ICI 182,780 is a fully effective pure antioestrogen in a primate.
Journal of Endocrinology (1992) 135, 239–247
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SUMMARY
The excretion of steroid hormone metabolites was studied in normal, thyrotoxic and myxoedematous subjects. Corticosteroid excretion was increased in thyrotoxicosis and reduced in myxoedema.
In myxoedema there was also a fall of total androgen excretion due principally to a reduction of the androsterone component.
There was no change in total androgen excretion in thyrotoxic subjects, but there was a fall of aetiocholanolone excretion.
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Blood samples, drawn every 15 days (September 1975–September 1976) from four laboratory-housed male mongrel dogs, were assayed by radioimmunoassay for levels of testosterone and LH in the plasma. The mean plasma concentrations of testosterone remained relatively constant for most of the year with the exception of a significant rise in late August and early September. Mean plasma levels of LH showed a cyclic pattern throughout the year which could be represented by a cosine function curve. However, this cyclic pattern of LH was not accompanied by cyclic changes in plasma levels of testosterone and there was no relationship between these two hormones during the period of 1 year. As the cyclic pattern of LH was altered, the plasma level of testosterone began to rise and reached its highest concentration. Since this alteration of the LH cycle occurred before the increased concentrations of testosterone, and since there was no relationship between these two hormones for the period of a year, we have concluded that there may be another hormone(s) involved which either alters the sensitivity of the canine testis to LH or alters the LH synthesis/release mechanism of the pituitary gland.
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Abstract
β-Endorphin (β-endo) (1–31) is the active opioid peptide product of pro-opiomelanocortin processing. Further post-translational modifications of β-endo(1–31) yield β-endo(1–27), (1–26) and their acetylated forms which are considered to be opiate receptor antagonists. Mechanistically, alteration in opiatergic properties is likely to result in the loss of a number of physiological functions including reproductive capacity. The purpose of this study was to determine whether there are changes in the way β-endo neurones process the peptide with age in female C57BL/6J mice. Pooled extracts of arcuate nucleus (ARC) and preoptic area (POA) of 3- to 4-month-old normally cycling (4–5 days at dioestrus), 12- to 13-month-old irregularly cycling (5–7 days at dioestrus), 23- to 24-month-old acyclic (in persistent dioestrus) animals were subjected to reversed-phase HPLC (n=4 experiments). Column fractions were assayed for β-endo-like-immunoreactivity by sequence-specific RIAs. The opiate receptor active as well as opiate receptor antagonist forms of β-endo were present in both ARC and POA at all three age groups although their ratios varied. β-Endo(1–31), the active opiate, was the predominant form in young animals. At middle age there was a threefold (P<0·05, ANOVA) increase in the antagonist forms of β-endo and this was associated with a significant (P<0·05, ANOVA) increase in the ratio of antagonist to active forms. This was accompanied by a trend toward an increase in acetylated forms of β-endo in middle-aged mice. HPLC profiles from hypothalami of old animals more closely resembled those of young females. The increase in the antagonist forms of β-endo at middle age may contribute to a decline of opiatergic influences in the female C57BL/6J mouse and suggest a mechanism whereby alterations in opiate influence over gonadotrophin control may occur.
Journal of Endocrinology (1995) 144, 405–415
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SUMMARY
Total exchangeable sodium, potassium and bromide space were measured by a triple isotope technique, and antipyrine space, body weight, plasma electrolyte concentrations and urine electrolyte excretion were determined before and after intramuscular injection of 0·5 mg. aldosterone 6-hourly for 6–8 days in nine convalescent men.
After the treatment with aldosterone there were mean increases in body weight of 2·5 kg., 2·5 1. in total body water, and of 3·0 1. in extracellular fluid volume; a slight decrease in intracellular fluid volume was not significant. The mean total exchangeable sodium increased by 463 m-equiv. and the mean cumulative urinary excretion of sodium decreased by 444 m-equiv. The sodium was retained in the extracellular fluid without significant change in exchangeable intracellular sodium. Mean total exchangeable potassium was reduced by 207 m-equiv. while mean cumulative urinary potassium excretion increased by 88 m-equiv. The potassium loss was entirely intracellular.
The main source of error arose from isotope counting. The coefficient of variation of the sample count minus the background exceeded ±3% in 18 out of 150 samples: these results were discarded. Sixteen of the inaccurate counts were due to low concentrations of sodium or potassium in the specimens.
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ABSTRACT
Endocrine profiles were examined in swine that had integrated and expressed a fusion gene consisting of mouse metallothionein-1 (MT) promoter fused to either a human (h) or bovine (b) GH structural gene. Eleven of 18 pigs that had integrated MT-hGH and eight of nine pigs that had integrated MT-bGH expressed the genes. The level of expression varied widely among pigs (14–4551 μg/l for MT-hGH and 23–1578 μg/l for MT-bGH). The level of expression varied over time within each pig with no general pattern. Concentrations of porcine GH (pGH) were lower in MT-hGH pigs that expressed the gene than in non-expressors or in littermate controls. Insulin-like growth factor-I (IGF-I) concentrations increased with age in all pigs and were raised threefold in pigs expressing either the MT-hGH or MT-bGH genes. Measurement of the foreign GH in samples taken at 15-min intervals failed to reveal any short-term fluctuations in concentration. Administration of hGH releasing factor (GRF) to pigs expressing MT-bGH resulted in attenuated release of pGH compared with that of contemporary controls. Concentrations of bGH did not change after GRF injection. Human and bovine GH expressed in transgenic pigs appear to be biologically active in that they induce IGF-I and suppress endogenous pGH secretion. The failure to find short-term fluctuations and the lack of response to GRF injections are consistent with a non-pituitary and non-GRF regulatable site of production.
Journal of Endocrinology (1989) 120, 481–488
