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M. G. Metcalf
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J. H. Livesey
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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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M. G. Metcalf
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J. H. Livesey
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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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MD Robertson
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G Livesey
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LM Morgan
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SM Hampton
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JC Mathers
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Glucagon-like peptide (7-36) amide (GLP-1) is an incretin hormone of the enteroinsular axis released rapidly after meals despite the fact that GLP-1 secreting cells (L-cells) occur predominantly in the distal gut. The importance of these colonic L-cells for postprandial GLP-1 was determined in healthy control subjects and in ileostomy patients with minimal small bowel resection (<5 cm). Subjects were fed a high complex carbohydrate test meal (15.3 g starch) followed by two carbohydrate-free, high fat test meals (25 g and 48.7 g fat respectively). Circulating levels of glucose, insulin, glucagon, glucose insulinotrophic peptide (GIP) and GLP-1 were measured over a 9-h postprandial period. For both subject groups the complex carbohydrate test meal failed to elicit a rise in either GIP or GLP-1. However, both hormones were elevated after the fat load although the GLP-1 concentration was significantly reduced in the ileostomist group when compared with controls (P=0.02). Associated with this reduction in circulating GLP-1 was an elevation in glucagon concentration (P=0.012) and a secondary rise in the plasma glucose concentration (P=0.006). These results suggest that the loss of colonic endocrine tissue is an important determinant in the postprandial GLP-1 concentration. Ileostomists should not be assumed to have normal enteroinsular function as the colon appears to have an important role in postprandial metabolism.

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MARY G. METCALF
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R. A. DONALD
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J. H. LIVESEY
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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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M. G. Metcalf
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V. Braiden
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J. H. Livesey
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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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S. L. Alexander
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C. H. G. Irvine
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J. H. Livesey
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R. A. Donald
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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

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T. J. MARTIN
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N. VAKAKIS
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J. A. EISMAN
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S. J. LIVESEY
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G. W. TREGEAR
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SUMMARY

Adenylate cyclase activity of crude plasma membranes from chick kidney was stimulated by low doses of parathyroid hormone (PTH). Sensitivity to PTH was ten to twenty times greater than that of a similar preparation from rat kidney cortex. Synthetic peptides consisting of the NH2-terminal 34 amino acids of bovine PTH (BPTH) and of human PTH (HPTH) were assayed, as were several analogues of these peptides. Bovine PTH (1–34) and HPTH (1–34) were equivalent in their action on chick kidney but the human peptide had only 20% of the activity of the bovine peptide on rat kidney cortex adenylate cyclase. Bovine proPTH ( −6→ + 34) and (Tyr1)-BPTH (1–34) had less activity than BPTH (1–34). Bovine PTH (2–34) inhibited the response to BPTH (1–34). Neither salmon calcitonin nor vasopressin stimulated adenylate cyclase activity.

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J. H. Livesey
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H. K. Roud
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M. G. Metcalf
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R. A. Donald
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First morning urine samples were collected from both menstruant and post-menopausal women and stored at −25 °C. Immunoreactive FSH disappeared from these samples (t½ = 30 days), ultimately stabilizing at about 20% of the initial value. The loss was more rapid at −20 °C and less rapid at −55 °C and +4°C. Immunoreactive LH was also lost from frozen urine, but more slowly than FSH. The addition of glycerol to urine (0·52 mol/l) stored at −25 °C prevented loss of immunoreactive FSH and LH for at least 105 days.

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