Bile salt biotransformations by human intestinal bacteria.

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age. The classical symptoms are those of hyperandrogenism (hirsutism, persistant acne, androgen dependent alopecia) together with symptoms of anovulation (infertility, amenorrhoea, irregular dysfunctional uterine bleeding).1In the last 10 to 15 years, the use of high resolution pelvic ultrasonography has greatly facilitated identification of polycystic ovaries in women with hirsutism or menstrual disturbance. It is now clear that the range of presenting symptoms of women with polycystic ovaries includes not only non-hirsute women with oligomenorrhoea or amenorrhoea but also hirsute subjects with regular, ovulatory cycles. PCOS occurs in nearly 75% of cases of anovulatory infertility and over 80% of subjects with hirsutism.1 The typical biochemical features of PCOS include hyperandrogenaemia and an increase of serum luteinising hormone (LH) (with normal follicle stimulating hormone) but PCOS is also associated with a characteristic metabolic syndrome that includes hyperinsulinaemia, insulin resistance, and dyslipidaemia.1-4 These features are linked to a significantly increased risk of type II (non-insulin-dependent) diabetes in later life and women with PCOS may also have a greater chance of developing premature cardiovascular disease.3 5 6 

The presence of polycystic ovaries is necessary for the development of the syndrome but not all women with polycystic ovaries have PCOS. The typical …

Polycystic ovary syndrome.

Various tumours, classically specified as either neuroendocrine or non-neuroendocrine, contain high numbers of somatostatin receptors, which enable in vivo localization of the primary tumour and its metastases by scintigraphy with the radiolabelled somatostatin analogue octreotide. In addition granulomas and autoimmune processes can be visualized because of local accumulation of somatostatin receptor-positive activated mononuclear leucocytes. In many instances a positive scintigram predicts a favourable response to treatment with octreotide. It is tempting to speculate that octreotide labelled with an appropriate radionuclide might be used in cancer therapy. The successful application of radiolabelled octreotide in scintigraphy indicates the possible usefulness of other radiolabelled peptides, either native peptides or derivatives of these, in, for example, nuclear oncology. The small size of these peptides, e.g. bombesin and substance P, is of the utmost importance for a relatively fast blood clearance, thus leading to low background radioactivity. In this way peptides are powerful alternatives to (fragments of) monoclonal antibodies, the application of which to scintigraphic localization of specific cell surface antigen-bearing tumours is plagued by slow blood clearance and, hence, high background levels.

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Somatostatin receptor scintigraphy with [111In-DTPA-d-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)61375-1.pdf

Cushing's syndrome

I. Introduction IN THE adult ovary, folliculogenesis starts when follicles leave the pool of resting follicles (RF) to enter the growth phase. From there, the early growing follicle undergoes a developmental process including a dramatic course of cellular proliferation and differentiation. In primates, only one follicle commonly reaches the preovulatory stage every cycle; most follicles fail to complete this maturation scheme, dying in the process termed atresia. In recent years, a picture has emerged depicting the classic endocrine control of ovarian function by LH and FSH, entangled in a maze of regulatory systems hinging on cell-cell interactions between follicular cells, via action of a variety of molecules (1–3). Different types of cell-cell interactions have been described. In paracrine regulations, a molecule synthesized by one cellular type is released into the interstitial milieu to act directly on another cellular type. In autocrine regulations, molecules synthesized by one cellular type are rel...

/pdf/regulation-of-ovarian-follicular-development-in-primates-4srrm0fi7f.pdf

Regulation of ovarian follicular development in primates: facts and hypotheses.

Acromegaly is usually regarded as a disease which arises sporadically except on those rare occasions in which it occurs as one component of an inherited pluriglandular syndrome Familial acromegaly occurring in isolation has been reported only rarely We have studied three families in each of which two first-degree relatives have developed acromegaly without clinical evidence of other endocrinopathies, in order to clarify the relationship of familial acromegaly to multiple endocrine neoplasia, type 1 (MEN 1) No further subclinical cases of acromegaly have been detected in those first-degree relatives of the index cases who were screened In two of the families, we have found no evidence of abnormal pancreatic or parathyroid function either in the acromegalic index cases or their asymptomatic relatives: a diagnosis of MEN 1 is therefore effectively excluded In the third family, the presence of multiple subcutaneous lipomata in several members of the family and elevation of PTH levels in two (normocalcaemic) acromegalic index cases, might indicate a highly atypical presentation of MEN 1 None of the six acromegalic index cases had elevations of circulating growth hormone releasing hormone levels We conclude that isolated familial acromegaly may be more common than has hitherto been realized and that, in these families at least, ectopic production of growth hormone releasing hormone is not responsible

Familial acromegaly: studies in three families

Hypersecretion of growth hormone (GH) is the principal feature of acromegaly and is accompanied by an excess of IGF-I production which mediates some of the actions of GH. The activity of IGF-I is modulated by a number of specific binding proteins (IGFBPs) which form complexes with IGF-I in the circulation. In this study, the technique of Western Ligand Blotting followed by 2-dimensional radioactive scanning was employed to investigate the correlations between relative levels of the IGFBPs and the main factors implicated in their regulation: IGF-I, GH and insulin, in a group of acromegalics with varying disease activity. The two glycosylated forms of IGFBP-3 correlated with increased levels of IGF-I (40.5 kD, r = 0.468, p < or = 0.01 and 36.5 kD, r = 0.809, p < or = 0.001), but did not relate to mean GH levels. Quantification of IGFBP-2 on the ligand blot showed an association with RIA levels of IGFBP-1 (r = 0.35, p < or = 0.05). IGFBP-1 RIA levels did not relate to the radioactivity in the assumed IGFBP-1 region of the ligand blot. This may be explained by fragments of IGFBP-3 running in this region and could account for the correlation seen between radioactivity in the 29 kD band with both forms of IGFBP-3 as well as with IGFBP-4. IGFBP-3 levels were normal in biochemically cured acromegalics with normal GH levels, although fasting insulin levels remained higher than normal (mean 16 +/- 4 vs normal 7.4 +/- 0.4 mU/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin-like growth factor binding proteins (IGFBPs) in acromegaly.

SUMMARY
The effects of the histamine (H2) receptor antagonist cimetidine on serum levels of prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH) and cortisol were studied in five normal males. Cimetidine, when given by infusion at the dose of 100 mg/h for 5 h, did not alter adenohypophyseal secretion either basally or after pituitary stimulation with LHRH and TRH. However, 400 mg cimetidine given intravenously as a bolus injection significantly stimulated PRL release in all subjects, without affecting any other measured hormone. A dose-response relationship existed, and 200 mg cimetidine seems to be the minimum PRL-releasing dose when given as an intravenous bolus injection. These results suggest that cimetidine releases PRL and that this effect is dose-related, but only when large intravenous injections are given.

Effects of the h2 receptor antagonist cimetidine on pituitary hormones in man

https://www.bmj.com/content/bmj/299/6708/1162.4.full.pdf

Gall stones and treatment with octreotide for acromegaly

Quinagolide (CV 205-502, Sandoz), an octahydrobenzo (g) quinoline, is a new non-ergot dopamine agonist which has specific D2 receptor activity and a long half-life, making it suitable for once-daily treatment. Recent uncontrolled reports have suggested that quinagolide may be successfully used for the clinical management of hyperprolactinemia with fewer adverse reactions than bromocriptine. This study is the first to compare quinagolide in a double-blind manner with bromocriptine, given only once-daily instead of the usual multidose regimen. In the first phase we compared, in 7 hyperprolactinemic patients, the effects over 24 h of a single oral dose of 0.05 mg quinagolide with 2.5 mg bromocriptine. Compared with placebo, both bromocriptine and quinagolide showed potent PRL-inhibiting and GH-releasing effects, with comparable effects at 24 h; no significant changes were observed in TSH, LH, FSH or cortisol. Twelve hyperprolactinemic patients were then randomized to receive either once-daily bromocriptine or quinagolide in incremental doses for a period of six months. Both drugs were found to be equally effective, and no differences were seen either in adverse reactions or PRL levels during repeated diurnal sampling. We therefore conclude that quinagolide and bromocriptine are therapeutically equivalent in long-term use, and both are equally effective when given once a day. However, some patients intolerant of bromocriptine may respond better to quinagolide, and vice versa.

Acute and long-term effects of once-daily oral bromocriptine and a new long-acting non-ergot dopamine agonist, quinagolide, in the treatment of hyperprolactinemia: a double-blind study.

J. A. H. Wass

Papers

Familial acromegaly: studies in three families

Insulin-like growth factor binding proteins (IGFBPs) in acromegaly.

Effects of the h2 receptor antagonist cimetidine on pituitary hormones in man

Gall stones and treatment with octreotide for acromegaly

Acute and long-term effects of once-daily oral bromocriptine and a new long-acting non-ergot dopamine agonist, quinagolide, in the treatment of hyperprolactinemia: a double-blind study.