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SUMMARY
Three trials, each using seventy-two ovariectomized Suffolk cross-bred ewes, were conducted to determine the interaction on the behavioural and vaginal response of varying the time of injection of oestradiol benzoate (ODB; dose levels 16, 20 and 25 μg in oil) relative to that of progesterone (six injections each of 6 mg in oil, spread over 3 days).
When ODB was injected before or during the period of progesterone treatment no ewe was served, and the vaginal response was partially suppressed. Maximal behavioural responses were observed when ODB was injected 24–48 hr after the final injection of progesterone. Responses decreased as this interval increased. Maximal vaginal responses were observed when ODB was injected 48 hr or more after the final injection of progesterone. Vaginal sensitivity did not decline with increase in this interval.
For assay purposes, using both criteria, it is necessary to inject oestrogen 48 hr after cessation of progesterone treatment in order to obtain a maximal response.
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SUMMARY
The vaginal smear pattern of the intact ewe experiencing normal oestrous cycles was compared with that of the spayed untreated ewe, and with the spayed ewe injected with a physiological dose-level of oestradiol benzoate (ODB) administered either alone or alternating with progesterone (Prog.) injected in a time-dose relationship closely approximating that of the intact animal.
Normal vaginal cornification appeared to be a result of oestrogen stimulation. The normal manifestation of leucocytic invasion and changes in the viscosity of mucus appeared to be dependent on an interaction between oestrogen and progesterone.
Some vaginal cornification was apparent on the day of oestrus, or 48 hr after the injection of ODB, but maximum cornification occurred 2 days later. For a maximum response, as measured by the number of ewes which yielded one or more cornified smears, it was necessary to take smears daily for 4 days commencing on the day of oestrus.
By relating the smear pattern of the ODB-injected spayed ewe to that of the normal intact ewe a standard method of appraisal of vaginal smears has been evolved. This is considered suitable for quantitative assay work. A positive vaginal smear is one which is virtually free of leucocytes but contains appreciable numbers of cornified cells either alone or in association with squamous and/or nucleated epithelial cells. The various types of typical cornified smears are illustrated.
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SUMMARY
Seventy-two spayed Suffolk cross-bred ewes were used in a series of six trials, conducted at intervals of 16 days and designed to determine the quantitative vaginal response to oestradiol benzoate (ODB) when injected either alone or alternated with progesterone given at the rate of 10 mg/day for 12 days.
The vaginal response to ODB when alternated with progesterone did not differ significantly from trial to trial. The vaginal response to ODB given alone showed a highly significant decline, with successive treatments, from a hypersensitive to a hyposensitive condition, clearly suggesting the development of a refractory state.
It appears, therefore, that in addition to its role in maintaining a constant and highly sensitive state of psychic reactivity to ODB, progesterone is involved in the maintenance of a uniform vaginal sensitivity to this hormone.
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Search for other papers by N. W. MOORE in
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SUMMARY
A flock of 135 ovariectomized ewes was used in five tests designed to investigate the ability of three 9α-halogenated steroids to condition the spayed ewe to exhibit oestrus after a single injection of oestradiol benzoate (ODB). The experimental steroids (9α-fluoro-11β-hydroxypregn-4-ene-3,20-dione, 9α-chloro-11β-hydroxypregn-4-ene-3,20-dione and 9α-bromo-11β-hydroxypregn-4-ene-3,20 dione) were tested against a progestagen of known characteristics (17α-acetoxy-9α-fluoro-11β-hydroxypregn-4-ene-3,20-dione = SC-9880, G. D. Searle) and against each other.
The steroids were injected intramuscularly, daily for 12 days and ODB was given at one of three doses as a single intramuscular injection 48 or 96 hr. after the final steroid injection.
The effects of the three experimental steroids, as indicated by the oestrous responses to ODB, differed little from that of SC-9880, thus proving them to be highly potent progestagens; 0·4 mg./day appeared to be about the minimum daily effective dose of all three experimental steroids indicating a potency about 15–20 times that of progesterone.
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SUMMARY
Four trials were conducted each with seventy-two ovariectomized Suffolk crossbred ewes, to determine the requirements of oestradiol benzoate (ODB) for behavioural and vaginal oestrus when, preceded by progesterone injections for periods of 3, 6 and 12 days. Effective daily requirements of progesterone were also determined.
There was no interaction between the daily dose-level or duration of stimulation by progesterone and the vaginal response to ODB. The respective values of ED50 and ED90 of ODB (in μg) for vaginal smears, with their associated 95% fiducial limits, were 8·4-10·7-12·1 and 16·8-18·6-21·9.
There was a progressive increase in sensitivity to ODB, as measured by oestrous behaviour, with increasing duration of progesterone pretreatment at daily dose-levels between 3 and 24 mg. The respective values of ED50 of ODB (in μg) injected following 3, 6 and 12 days' effective pretreatment, with their associated 95% fiducial limits, were 17·0-18·7-20·5, 14·8-15·7-16·6 and 11·9-13·1-14·5. The respective values of ED90 were 24·5-27·0-30·7, 20·9-22·6-25·3 and 17·0-18·9-22·0.
The requirement of ODB to induce behavioural oestrus in 90% of ewes, after pretreatment with progesterone for 12 days, was indistinguishable from that needed for characteristic vaginal changes. This clearly suggests a close approximation to physiological time-dose relationships.
The effective daily dose of progesterone, for maximum oestrous response, lay between the limits of 3 and 12 mg administered as a divided dose. A daily dose of 24 mg appeared slightly less effective, while 1·5 mg/day was much less effective.
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Division of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada
(Received 13 June 1977)
Several lines of circumstantial evidence suggest that the neurohypophysial hormones may be biosynthesized in the form of larger peptides (prohormones) which are degraded to the free hormones during passage of the neurosecretory granules from the hypothalamus to the neurohypophysis (Vogt, 1953; Sachs & Takabatake, 1964; Pickering, Jones & Burford, 1971). Furthermore, it has been suggested that the hormone carrier proteins, the neurophysins, may at some stage in the biosynthesis, form part of the putative prohormones (Hope & Pickup, 1974).
In cattle, arginine-vasopressin (AVP) is associated with bovine neurophysin II (Dean, Hope & Kazič, 1968), the complete amino acid sequence of which has been elucidated by Schlesinger, Capra & Walter (1974) and Wuu & Crumm (1976). In the present study, two dodecapeptide analogues of AVP in which the peptide chain was elongated
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In the golden hamster, there are marked sex differences in the Harderian gland. Male glands (which are heavier than female glands) possess two cell forms (Type I and Type II cells); female glands only exhibit the former. Female (but not male) glands contain large amounts of porphyrin, which are readily visible as solid depositions within the lumina.
The weight, histology and porphyrin content of the Harderian gland was examined in intact adult male hamsters and in male hamsters castrated for 1, 2 or 8 months. Castration resulted in a significant reduction in the weight of the gland, the disappearance of Type II cells, and the presence in the gland of solid porphyrin accretions. The levels of copro- and (especially) protoporphyrin were greatly increased. These changes were more marked with time after castration. When the ability of diverse androgens (testosterone, 5α-dihydrotestosterone, androst-4-ene-3,17-dione (androstenedione), dehydroepiandrosterone and androsterone) to prevent these changes was tested, testosterone and androstenedione maintained glandular weight. All the androgens maintained normal frequencies of Type II cells and all except dehydroepiandrosterone prevented deposition of porphyrin. The potencies of the various androgens in maintaining normal Harderian gland morphology and activity are compared with their effects on other somatic variables and sexual behaviour.
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SUMMARY
In pregnant ewes the progesterone concentrations in plasma from the maternal jugular, ovarian (active ovary) and uterine veins and from the foetal umbilical vein were measured by a competitive protein-binding technique.
Peripheral plasma levels remained fairly uniform throughout pregnancy, whereas ovarian levels dropped at about the 130th day of pregnancy. Uterine plasma levels were low until the 80th day; foetal levels rose as pregnancy progressed.
The major sources of progesterone appeared to be the ovary (corpus luteum) and the uterus (placenta). The ovarian contribution was greater during the first two-thirds of pregnancy than later, whereas that made by the placenta was lower during the first one-third of pregnancy.
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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
The effect of insulin-like growth factor-I (IGF-I) administration on body weight gain and the rate of recovery of renal function was investigated in rats following an acute episode of renal ischaemia. Since the des(1–3)IGF-I and LR3IGF-I variant forms of IGF-I have been shown to be more potent than IGF-I, their effects were also examined. Acute renal failure was produced in male Sprague–Dawley rats by clamping both renal arteries for 45 min. Treatment was commenced at the time of renal artery occlusion with vehicle (0·1 mol acetic acid/l; control group), IGF-I (2·0 mg/kg per day), des(1–3)IGF-I (2·0 mg/kg per day) or LR3IGF-I (1·5 mg/kg per day) by s.c. osmotic pump, and continued for 7 days, with rats being held in metabolism cages. Glomerular filtration rate (GFR) was estimated by the use of 51Cr-EDTA continuously infused i.p. via osmotic pump. Following the episode of renal ischaemia, body weight gain and nitrogen retention were significantly improved in all three peptide-treated groups, and serum urea concentrations were reduced in the groups treated with IGF-I and des(1–3)IGF-I. However, there was no evidence of the variants having any increased potency over the growth effects of IGF-I itself. GFR was significantly reduced, urine output was increased and urinary concentrating ability was reduced in all groups compared with normal rats, with no significant effect of the IGF peptides being apparent.
A closer examination of the acute effects of LR3IGF-I on renal function was undertaken by measuring GFR for 3 days before and 3 days after renal ischaemia in two groups of rats, treated for the latter 3 days with either vehicle (controls) or LR3IGF-I (1·5 mg/kg per day). LR3IGF-I treatment following renal ischaemia resulted in a significantly greater fall in GFR than in controls, urinary osmolality was also significantly reduced, and fractional excretion of sodium was increased. In addition, there was histological evidence of a greater degree of tubular epithelial calcification in the kidneys of the rats treated with LR3IGF-I.
This study showed that administration of IGF peptides at doses sufficient to cause significant improvement in anabolic status did not improve renal function in rats following an acute episode of renal ischaemia. Indeed the LR3IGF-I variant of IGF-I had a deleterious effect on renal function in the early stage of the recovery period.
Journal of Endocrinology (1994) 140, 23–32
