ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb03762.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummarySix patients with mastalgia were treated with polylactide/ glycolide SO: 50 implants containing 6 6 mg buserelin once every 4 weeks, to study the relationship between buserelin pharmacokinetics and suppression of pituitary‐ovarian function. On the first treatment day there was an initial rise in plasma and urinary buserelin levels followed by a rapid fall during the next 2 days. After a plateau phase (60–80 μg/g creatinine) urinary buserelin/creatinine ratios decreased slowly to a mean value of 25 μg/g creatinine 4 weeks after Implantation. Plasma oestradiol concentrations dropped to castrate values within 2 weeks of treatment reaching a mean concentration of 17 pmol/l compared to 27 pmol/l (P5 μg/g creatinine) during more than 8 weeks followed by an exponential decrease (half‐life of buserelin release: 15 days) to undetectable buserelin levels at 16–22 weeks after the last implantation. A rise of suppressed plasma oestradiol concentrations to above castrate levels was found 15–20 weeks after the last buserelin Implantation, at a time when urinary buserelin excretion had decreased below 0.2 μg/g creatinine. It Is concluded that after initial suppression of pituitary‐ovarian function only very low concentrations of buserelin are needed to maintain suppression of ovarian activity by using slow relea

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb03763.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummaryIn‐vivo and in‐vitro studies have provided evidence that a non‐steroidal ovarian factor, called gonadotrophin surge attenuating factor (GnSAF), attenuates the endogenous LH surge in superovulated women. To study the mechanism of action of GnSAF, the LH response to two i.v. pulses of GnRH (10μgeach, 2 h apart) was investigated in eight normally ovulating women during the late follicular phase of a spontaneous and an FSH superovulated cycle. The maximal LH increase in response to the first pulse (initial release) was considered as representing the acutely releasable pool and the δLH area under the whole curve (integrated response) the reserve pool of LH. Both the initial release and the integrated response to GnRH were markedly attenuated in the FSH as compared to the spontaneous cycles. The response to the second pulse was significantly greater than the response to the first pulse (self‐priming effect of GnRH) in both the spontaneous and the FSH cycles. However, in the FSH cycles the self‐priming effect of GnRH was markedly reduced as compared to the spontaneous cycles. We conclude that during superovulation induction in women the two pools of pituitary LH are markedly attenuated. It is suggested that GnSAF attenuates both the GnRH‐induced initial release of LH and the self‐priming effect of GnRH o

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb03764.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummaryHypochondroplasia, a heterogeneous and usually mild form of chondrodystrophy, is a common cause of short stature. It often goes unrecognized in childhood and is diagnosed in adult life when disproportionate short stature becomes obvious.We performed restriction enzyme analysis of the Insulinlike growth factor I (IGF‐I) gene on the families of 20 white British Caucasian children with short stature attributed to hypochondroplasia by radiological and clinical criteria, who were undergoing human growth hormone (r‐hGH) treatment, in 60 children with Isolated growth hormone deficiency and in SO normal Individuals. The frequency of the heterozygous pattern (Hind III: 8.2, 5.2, 4.8, 3.2 kb fragments, Pvu: 8.4, 5.1, 4.7, 2.5 kb fragments) in children with hypochondroplasia was significantly higher(X2:P<0.05)than in the control groups. The hypochondro‐plastic children whose response to r‐hGH treatment was characterized by a proportionate Increase in both spinal and sublschial leg length were all heterozygous for two co‐inherited IGF‐I gene restriction fragment length polymorphism (RFLP) alleles (Hind III: 5 2,4 8 kb; Pvu II: 5 1,47 kb). Children whose response was characterized by accentuation of the body disproportion by r‐hGH treatment were all homozygous for these alleles (Hind III: 4 8,4 8 kb; Pvu II: 4.7, 4.7 kb). Their response to r‐hGH treatment is significantly different (P<0.01). Studies of the families of the heterozygous affected children demonstrated strong linkage (lod score 3 311 at zero recombination) of the IGF‐I gene locus at chromosome 12q23 to this subgroup of hypochondroplasia. The 5 2 kb Hind III and 51 kb Pvu II alleles are in strong linkage disequilibrium with this trait. These data indicate that IGF‐I gene may be a candidate gene for involvement in the aetiology of short stature presenting with hypochondroplastic features and a proportionate response to r‐hGH treatment; they also provide support for the concept of genetic heterogeneit

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb03765.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummaryAcromegaly is characterized by a hypersecretion of GH, which in turn results in an excess of IGF‐I, an important mediator of its actions. IGF‐I itself is intimately related to insulin both in structure and function. IGF‐I circulates associated with specific binding proteins which appear to have Important effects on its activity. We have examined the inter‐relations between GH, prolactin, insulin, IGF‐I and one of the binding proteins, IGFBP‐1, in 62 patients with acromegaly of varying activity. Serum IGF‐I levels were closely related to the logarithm of mean GH levels (r = 0.76; n = 62; P<0.001) but multiple regression analysis suggested that, after accounting for the variation due to GH, insulin accounted for some of the additional variation of IGF‐I. IGF‐I concentrations were independent of prolactin. Fasting Insulin levels were high and unrelated to mean GH levels but correlated with those of IGF‐I (r = 0.542;n = 57;P<0.001). This correlation coefficient was further improved by also accounting for variations in IGFBP‐1 (r = 0.684; n = 57; P<0.001). Even In subjects whose acromegaly was well controlled or cured, as indicated by GH levels of<1 mU/l or IGF‐I levels of<2 U/ml, fasting insulin levels remained significantly elevated in some individuals. The reason for this persistent abnormality is not clear. Fasting IGFBP‐1 levels were low and unrelated to mean GH but were Inversely related to fasting insulin levels (r=−0.593; n = 57; P<0.001). We propose that a cascade of events occurs In acromegaly. GH hypersecretion causes chronic elevation of IGF‐I levels which In turn could lead to increased pancreatic insulin production. This raised insulin could then have additional effects, raising IGF‐I levels further and lowering IGFBP‐1; the latter could then r

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb03766.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummaryThis study evaluated whether pharmacological doses of recombinant human growth hormone (hGH) influences androgen or Cortisol metabolism during nutritional repletion following prolonged illness. Stable hospitalized adults (three male, seven female) receiving constant calorie and protein intake were studied. An initial control week was followed by a treatment period during which hGH (10 mg/day s.c.) was administered daily. Prior to hGH treatment, serum and 24‐h urinary concentrations of dehydroepiandrosterone sulphate (DS) were below the normal range; serum androstenedione and testosterone concentrations were within the lower limit of normal. In contrast, serum Cortisol (F) and 24‐h urinary F excretion were normal. During hGH treatment, nitrogen balance became positive and plasma insulin‐like growth factor I (IGF‐I) concentrations rose five to seven‐fold. However, serum DS, androstenedione, testosterone and F, and urinary F excretion did not change, while 24‐h urinary DS excretion fell significantly. Growth hormone administration markedly stimulated protein anabolism but did not increase the low concentrations of circulating androgens or alter the disassociation between adrenal androgen and F release in stable hospitalized males and females. Thus, hGH does not appear to function as a cortical adrenal androgen stimulating hormone (CASH) or regulate adrenal Cortisol or gonadal androgen release in this clini

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb03767.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummaryThe prolactin (PRL) response to fenfluramine (FEN), a serotonin (S‐HT) releasing agent, is used as an index of 5‐HT sensitivity in studying disorders associated with central S‐HT abnormality. Plasma oestrogen levels are known to augment PRL responses to a variety of stimuli. In order to examine the effect that ovarian steroids have on this response nine, healthy women were tested twice at three time points in the menstrual cycle: early follicular, mid‐cycle and late luteal phase with either d‐FEN, a more specific 5‐HT agent than the racemic mixture, or placebo. Responses to d‐FEN were maximal at mid‐cycle, lowest during the early follicular phase, with responses premen‐strually being intermediate between the two. Responses to placebo did not vary. Plasma oestradiol levels fluctuated In parallel with neuroendocrine responses to d‐FEN. The possible mechanisms are discussed, Including an effect that oestradiol may exert at cent

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb03768.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummaryWe report a cluster of male pseudohermaphrodites from the Simbari Anga linguistic group in the Eastern Highlands of Papua New Guinea. These subjects are born with a rudimentary clitoral‐like penis and pseudovaginal perineoscrotal hypospadias. At puberty, the penis enlarges with concurrent growth of pubic and axillary hair and significant muscular development. There is significant facial hair, but it is less than that of their normal male siblings or other male relatives. Plasma collected from four adult subjects revealed elevated plasma testosterone levels, low to low normal dihydrotestosterone levels, and elevated testosterone/dihydrotestosterone ratios. All subjects had high urinary aetiocholanolone/androsterone ratios, and C12andC215β/5αmetabolite ratios. Decreased 5ot‐reductase activity was demonstrated in fibroblasts cultured from genital skin. The data indicate a phenotypic and biochemical profile similar to patients studied in the Dominican Republic, except tor a greater abundanceoffacial and body hair. The phenotypic variability, as pertains to facial and body hair, may be related to differences in familial expression, as well as the degree of enzyme deficiency. Infants, thought to be females at birth, were reared as girls until puberty in a society practising one of the strictest gender segregations known. At puberty, these ‘girls’ were discovered to be boys, and a switch of gender roles was instituted. Recently, however, some Muniri, Dunkwi and northern Simbari hamlets recognize these individuals as male in infancy and rear them as boys, calling them ‘kwalatmala’ to distinguish them from normal males, accepting them as an intersex destined to occupy mal

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb03769.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummaryThe reports of the effect of calcitonin on pituitary function are confusing and often refer to uncontrolled studies. We have now carried out a double‐blind placebo‐controlled trial of Intravenous and subcutaneous salmon calcitonin on anterior pituitary function in 17 healthy volunteers. Visual analogue scores for the nausea and vomiting seen after salmon calcitonin correlated with the rise in ACTH and, secondarily, Cortisol. Calcitonin had no effect on growth hormone, prolactin, thyrotrophin, luteinizing hormone or follicle stimulating hormone. It is concluded that the stimulation of ACTH secretion following a single dose of salmon calcitonin Is probably the result of the stress of nausea rather than a direct effect on the pituit

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb03770.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummarySerum androgen levels were studied In 100 patients (50 male) with varying degrees ot severe illness, determined by Acute Physiological and Chronic Health Evaluation (APACHE). Comparison with normal subjects revealed the following changes:1Basal dehydroeplandrosterone sulphate (DHEAS) values were decreased in the ill female patients (P<0.001) as well as in the III males (two groups, P<0.01; P<0.05). Androstenedione values did not differ from the controls in patients of either sex. Basal testosterone levels were decreased in ill male patients (P<0.001), but not in females.2The low testosterone concentrations in the severely ill male patients correlated Inversely with the APACHE score; additionally, a dependence on diagnostic categories could be demonstrated In men, since the lowest values were found in patients suffering from sepsis or liver cirrhosis. Acutely ill males had a moderately decreased testosterone, whereas chronically ill males showed a marked reduction of testosterone compared to the controls. Lowered DHEAS and androstenedione levels could be measured in chronically ill males but not In III females.317α‐OH‐progesterone and 17α‐OH‐pregnenolone levels in subgroups of the patients suggested a probable enzymatic block In the A5‐pathway of androgen biosynthesis in severe illness. The ratio of 17α‐OH‐pregnenolone to DHEAS was significantly higher in male patients and tended to be high in ill females, whereas the ratio of 17α‐OH‐progesterone to androstenedione showed no difference between hea

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb03771.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY