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Search for other papers by M. G. Metcalf in
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Search for other papers by J. H. Livesey in
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ABSTRACT
In normal women reproductive capacity diminishes with age; the decline has been detected before the start of the menopausal transition. It is known that in premenopausal women most menstrual cycles are ovulatory. An investigation was set up to examine the possibility that there is an age-related decline in the ability of the corpus luteum to secrete progesterone at this time.
Once-weekly urine samples for the measurement of pregnanediol were collected from 100 women aged 20–48 years, all of whom had regular 20- to 35–day menstrual cycles (1124 samples collected during the course of 312 menstrual cycles of which 96·8% were ovulatory). Pregnanediol excretion rates parallel the levels of progesterone in plasma. Examination of the rank correlation between age and pregnanediol excretion identified a significant negative correlation during the early and mid-follicular phases, but failed to detect any age-related change during the luteal phase.
The evidence does not support the concept of an age-related increase in luteal phase defects before the start of the menopausal transition.
J. Endocr. (1988) 119, 153–157
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ABSTRACT
In normal women the menopausal transition starts typically with a sudden break in regular menstrual cyclicity: gonadotrophin levels escape from the cyclical pattern characteristic of fertile women and increasingly rise into the postmenopausal range. An investigation was undertaken to determine whether this rise precedes the first appearance of ovarian dysfunction.
Weekly urine samples for the measurement of FSH, LH and pregnanediol were collected from 100 women, all of whom had regular 20- to 35-day menstrual cycles (504 samples from 48 women aged 20–39 years and 620 samples from 52 women aged 40–48 years; 96·8% of these cycles were shown to be ovulatory).
Excretion rates of FSH in excess of 5 i.u./24 h occurred more often in women aged ≥ 40 years than in younger women (incidence, 31·5 cf. 19·5%; P < 0·001). The difference was greatest at the time of the perimenstruum (7-day incidence, 32·5 cf. 13·9%) and declined to insignificance during the mid-cycle gonadotrophin surge (7-day incidence, 44·2 cf. 34·8%). Examination of the rank correlation between age and gonadotrophin excretion confirmed the age-related rise in FSH and identified a lesser but significant perimenstrual rise in LH. For both FSH and LH these changes were small compared with the increases observed in nine women presumed to have reached the menopausal transition during the trial (incidence FSH ≥ 5 i.u./24 h, 60·6%; incidence LH ≥ 5 i.u./24 h, 48·6%).
It is concluded that in fertile women there is evidence of an age-related rise in FSH which is distinct from the changes occurring at the start of the menopausal transition.
J. Endocr. (1985) 105, 357–362)
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ABSTRACT
Normal human peripheral plasma, examined by direct radioimmunoassay corticotrophin-releasing factor (CRF) using seven different antisera, showed marked inhibition of tracer binding to antiserum. This apparently high Cimmunoreactiv(CRF-LI) dilute in parallel with synthetic human CRF-41.parison, most equine and ovine plasma samples had low Cconcentrations.ractionation of both normal and late pregnancy human plasma on SG-75 neutral pH indicated the majority of the CRF-LI of large molecular size. The molecular weight was estimated to be approximately 29 000 following chromatography human plasma on Sephacryl S-200.igh CRF-LIrmal plasma was reduced to barely detectable levels by methanol treatment despite the recovery of added human CRF-41 of >80%. Methanol extracts of late pregnancy human plasma, however, retained high CRF-LI which exhibited the immunoreactive and Sephadex elution characteristics of synthetic human CRF-41. 125I-Labelled human CRF-41 added to human plasma showed a reversible, time-dependent alteration in molecular size and reduction in binding to excess antiserum. These findings indicate that direct RIA of human CRF in unextracted plasma leads to spurious results and suggest the presence in human plasma of an interfering factor and/or binding substance that is not generally apparent in equine or ovine plasma under the conditions described.
J. Endocr. (1988) 117, 299–307
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Abstract
Immunoreactive corticotrophin-releasing hormone (irCRH) was present in methanolic extracts of equine peripheral blood and showed no elevation in maternal peripheral serum in late gestation (0·54 ±0·25 pmol/l; mean ± s.d.) compared with control horses (0·41 ± 015 pmol/l). The irCRH of methanolic extracts of pituitary venous plasma had a similar elution position following reverse-phase HPLC to synthetic human CRH(1–41) and to irCRH released from horse stalk-median eminence tissue incubated in vitro. Gel chromatographic studies showed no evidence for a plasma CRH-binding protein (CRHBP) analogous to that found in human plasma in either peripheral blood from normal or pregnant horses or in pituitary venous plasma sampled from a cannulated horse. CRH-binding activity was detectable in peripheral plasma from one horse, however the molecular size of this was indicative of a γ-globulin rather than the 37 kDa CRHBP.
These studies suggest that, unlike in the human, CRH does not rise to high values in late gestation nor circulate in a bound form in equine plasma.
Journal of Endocrinology (1994) 143, 455–460
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A sensitive and specific radioimmunoassay developed for measuring the met-enkephalin analogue d-ala2-met(0)5-ol-enkephalin (DAMME) was used to study the pharmacokinetics of DAMME in the circulation of sheep. Plasma concentrations of DAMME were measured at varying time-intervals after an intravenous bolus injection or following a constant intravenous infusion of the analogue. The mean metabolic clearance rate of DAMME was 2·8 ml/min per kg, the mean circulating half-life was 52 min and the mean volume of distribution was 190 ml/kg. The longer circulating time of the analogue when compared with that of naturally occurring met-enkephalin would appear to explain its prolonged analgesic effect.
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The Medical Unit, The Princess Margaret Hospital, Christchurch 2, New Zealand
(Revised manuscript received 21 August 1978)
The frequent clinical and research requirement for measurement of both plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) has prompted the development of a simultaneous radioimmunoassay for these two hormones. The considerable advantages of a simultaneous method include an economy of plasma volume, assay reagents, test-tubes and, more importantly, the time required for radioactive counting and performance of the assay by technical staff. The latter two factors comprise a significant proportion of radioimmunoassay operating costs.
This report describes a simultaneous radioimmunoassay based on the use of 131I-labelled FSH, 125I-labelled LH, anti-FSH serum M93 6873 (a generous gift from Professor W. R. Butt, Birmingham), anti-human chorionic gonadotrophin (HCG) serum for LH measurement (Donald, 1972) and donkey anti-rabbit precipitating serum (Wellcome Reagents, U.K.) for separation of antibody-bound and free hormones. Pituitary gonadotrophin standard (LER 907)
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ABSTRACT
In order to assess the physiological importance of endogenous arginine vasopressin (AVP) in augmenting the ACTH response to corticotrophin-releasing factor (CRF), the response to CRF during hypertonic saline infusion in six Coopworth sheep was examined. A 4-h infusion of 5% (w/v) NaCl (3·8 ml/min) resulted in significantly (P < 0·01) greater rises in ACTH and cortisol, but not aldosterone, than were observed after CRF alone. Infusion of hypertonic saline without CRF resulted in a highly significant (P < 0·001) rise in plasma osmolality and AVP but no significant change in plasma ACTH, cortisol or aldosterone.
It is concluded that a marked but physiological increase in peripheral (and presumably central) levels of AVP does not result in any demonstrable change in plasma ACTH concentration. However, under these conditions, the ACTH and cortisol responses to CRF are considerably augmented.
J. Endocr. (1986) 108, 309–312
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Urine for the analysis of pregnanediol, oestrogens, FSH and LH, was collected weekly from 50 normal menstruant women. Twenty of these women were aged ≥ 40 years and had a history of regular menstrual cycles; they are termed premenopausal. The other 30 reported a recent break in regular cyclicity and are termed perimenopausal. All menstrual cycles observed in the premenopausal women were ovulatory in type and 25–30 days in length. The 124 cycles observed in the perimenopausal women were 18–260 days in length (median, 29 days), with 52% of the ovulatory type. To describe this diversity, a systematic classification is proposed based on (1) the excretion of pregnanediol in the 12 days preceding menstruation (classes I–IV), (2) gonadotrophin output (categories A–E, and L), and (3) the length of the menstrual cycle in days. The premenstrual surge of pregnanediol was greatest in class I cycles and diminished progressively until it became undetectable in class IV. Gonadotrophin excretion was lowest in category A cycles and increased progressively until all levels were within the postmenopausal range by category E. In cycles of category L only LH (and not FSH) was raised.
In the perimenopausal women 37 cycles included episodes of high gonadotrophin excretion (categories C–L), a phenomenon which was not seen in the premenopausal women. These cycles were usually longer than 50 days and were often anovulatory in type (classes II—IV). Typically they began with the high gonadotrophin levels and the low oestrogens which characterize the postmenopausal state, and ended after a rise in oestrogen output to levels ≥ 70 nmol/24 h. It is concluded that 'anovulatory' cycles and cycles in which there are 'postmenopausal' levels of FSH and LH are common in the perimenopause and that they are rare in premenopausal women.
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ABSTRACT
What are the long-term effects of hysterectomy on the ovaries of normal women? Ninety-three women aged 29–44 years (median, 38 years) who had undergone hysterectomy for benign reasons 0·3–9·1 years prior to investigation, contributed urine samples twice weekly for a period of 53–149 days (median 102 days) for pregnanediol analysis. The interval between successive pregnanediol peaks and their increment over baseline were measured.
The median peak interval was 27·3 days, and 93·3% of all intervals were of 21- to 35-days duration. Of the 337 peaks observed, 96·7% met the criteria previously used to define an ovulatory cycle. These are similar to the figures reported for menstruant women of comparable age. ANOVA showed no significant effect of age or time since hysterectomy on either the interval between peaks or peak increment (P > 0·10 in all cases). The evidence suggests that the ovaries of women who have no uterus behave like those of intact women.
Journal of Endocrinology (1992) 135, 597–602
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ABSTRACT
A non-surgical, non-stressful technique was used for collection of pituitary venous blood from five conscious horses every minute for two 10-min periods before and during isolation from the herd, which caused a predictable, yet humane and physiological, emotional stress. Pituitary blood was also sampled every 5 min for two approximately 90-min periods before and after isolation, while jugular blood was sampled every 15 min throughout the experiment.
During isolation, all horses became agitated, hyperventilating and sweating. Packed red cell volume increased, as did pituitary venous concentrations of adrenaline (mean ± s.e.m. concentration before isolation, 621·5±112·3 pmol/l; peak during isolation, 2665·4 ± 869·8 pmol/l; P <0·05) and noradrenaline (before, 871·8 ± 111·8 pmol/l; peak, 2726·1 ± 547·4 pmol/l; P<0·02). Concentrations of arginine vasopressin (AVP) were higher in pituitary venous but not in jugular blood during isolation than during the preceding 10-min period (P <0·05). Although AVP secretion increased in all horses, in three of the five it rose dramatically in the first minute of isolation to 25·7 (horse 1), 13·6 (horse 4) and 145·1 (horse 5) times the level in the last sample collected before isolation. Mean pituitary venous concentrations of ACTH and α-MSH increased during isolation in the three horses which had large increases in AVP secretion, but, overall, stress did not significantly affect ACTH or α-MSH secretion. Similarly, mean jugular cortisol levels were not significantly altered by isolation. However, the magnitudes of ACTH, AVP and α-MSH responses to isolation were negatively correlated with the jugular cortisol level before isolation. The changes in pituitary venous concentrations of ACTH and AVP were synchronous under resting conditions, whether samples were collected at intervals of 1 (P <0·01) or 5 (P <0·005) min; however, this synchrony was lost during isolation. The changes in pituitary venous concentrations of ACTH and α-MSH were synchronous both at rest (P <0·025 for 1-min sampling, P <0·01 for 5-min sampling) and during isolation (P<0·01).
We conclude that isolation stress increases AVP secretion and may alter the temporal relationship between pituitary venous concentrations of AVP and ACTH. Furthermore, the magnitude of the responses of AVP, ACTH and α-MSH to isolation is significantly affected by the prevailing cortisol level.
J. Endocr. (1988) 116, 325–334
