In order to investigate the involvement of prolactin-dopamine and dopamine-gonadotropin interactions in the hypothalamo-pituitary axis of hyperprolactinemia, in vitro studies were performed using primary cultures of dispersed rat hypothalamic heterogeneous cells containing tubero-infundibular dopaminergic neurons or gonadotropin-releasing hormone (GnRH) neurons. We observed that prolactin caused dose-dependent stimulation of [3H]dopamine release after a 16-h incubation. Staurosporin (10 nmol/l), an inhibitor of protein kinase C, significantly reduced the [3H]dopamine release induced by prolactin (1 mg/l). Incubation of tubero-infundibular dopaminergic neurons with prolactin (1 mg/l) had no effect on intracellular cyclic adenosine monophosphate accumulation. Dopamine (1 mumol/l) significantly (p < 0.01) reduced the release of GnRH induced by 50 mumol/l calcium ionophore from dispersed hypothalamic cells from the preoptic area, while prolactin had no effect on GnRH release. These data support the hypothesis that the antigonadotropic effect of prolactin on the hypothalamus is mediated by an inhibitory effect of dopamine on GnRH release.

A patient with acromegaly and hyperthyroidism due to a growth hormone-, thyrotrophin- and alpha-subunit-secreting pituitary adenoma is described. His decreased father had suffered from a pituitary tumour, and was likely to have had acromegaly as well. Plasma growth hormone and insulin-like growth factor I concentrations were elevated, with levels between 10 and 20 micrograms/l and 4.4 and 7.3 kU/l, respectively. In spite of hyperthyroidism (free thyroxine, 45 pmol/l; free triiodothyronine, 24 pmol/l), plasma thyrotrophin remained at 2.8 mU/l without any response to thyrotrophin-releasing hormone and could not be suppressed with exogenous administration of triiodothyronine. Plasma alpha-subunits were raised to 3.3-3.7 U/l (normal 0.4-1.1 U/l). Pathological examination of the surgically removed tumour showed a pituitary adenoma with the immunohistochemical presence of growth hormone, thyrotrophin, prolactin and alpha-subunit. This is the first report of a growth hormone-, thyrotrophin- and alpha-subunit-producing pituitary adenoma, which occurred in a familial setting.

The characteristics of the human serum growth hormone-binding protein (GHBP) were compared with those of a water-soluble GH-binding site prepared by incubating cultured IM-9 lymphocytes in assay buffer with 25 mmol/l iodoacetamide. High-performance liquid chromatography gel filtration of the water-soluble GH-binding site incubated with 125I-labeled human GH ([125I]hGH) revealed a large peak of bound [125I]hGH eluting at the same position as the peak of [125I]hGH bound to the GHBP in serum. The estimated M(r) of the peak was 120,000, presumably representing one [125I]hGH bound to two binding sites. The binding specificities of the serum GHBP, the water-soluble GH-binding site and the GH receptor on IM-9 lymphocytes were identical. The binding affinities for 22,000 hGH and for 20,000 hGH of the serum GHBP were similar to the binding affinity of the water-soluble GH-binding site but lower than those of the cellular GH receptor. These findings show that the characteristics of the serum GHBP are comparable to those of the water-soluble GH-binding site released from IM-9 cells and support the hypothesis that in man the serum GHBP is produced by proteolytic cleavage of the cellular GH receptor.

It has been reported that growth hormone modulates serum levels of insulin-like growth factor I (IGF-I) positively and serum levels of sex-hormone-binding globulin (SHBG) negatively. We have measured IGF-I and SHBG concentrations in 24 prepubertal patients with growth hormone deficiency. Twelve of these patients had had intracranial tumors removed (organic growth hormone deficiency) and 12 had growth hormone deficiency of unknown etiology (idiopathic). Fifty-two prepubertal control subjects, admitted for elective surgery, were also studied. All prepubertal patients were divided into two age groups: older and younger than 7 years of age. In both groups there were patients with multiple pituitary deficiencies on hydrocortisone and/or levothyroxine sodium replacement therapy. In the age group younger than 7 years, serum IGF-I was not significantly different between organic and idiopathic growth hormone deficiency (0.28 +/- 0.21 versus 0.062 +/- 0.071 mU/l) but serum SHBG levels were different (74.6 +/- 33.5 versus 173 +/- 59 nmol/l, p < 0.05). These values were not significantly different from controls (0.47 +/- 0.25 mU/l and 132 +/- 47 nmol/l, respectively). In the age group older than 7 years, there was no significant difference between organic and idiopathic growth hormone deficiency in serum IGF-I (0.33 +/- 0.17 versus 0.16 +/- 0.11 mU/l) or serum SHBG (113 +/- 72 versus 108 +/- 17 nmol/l). These values were significantly different from controls (1.04 +/- 0.36 mU/l and 68.7 +/- 31.7 nmol/l, p < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoreactive basic fibroblast growth factor (bFGF) could be isolated from the cytosol preparation of isolated porcine thyroid follicles as well as in the conditioned medium from thyroid follicles in suspension culture. A double band with 16,500 and 15,500 D was detected on sodium dodecyl sulfate polyacrylamide gel electrophoresis. In dot blot and western blot the isolated peptide was immunoreactive with a specific anti-bovine bFGF antibody. For further biochemical characterization, bFGF was isolated from entire porcine thyroid glands by ammonium sulfate precipitation, cation exchange chromatography and heparin affinity chromatography. The material obtained from all three origins was identical concerning affinity to heparin and immunoreactivity with the specific anti-bovine bFGF antibody and induced neovascularization in the chorioallantois membranes of chick embryos. Amino acid sequence analysis of the 16-amino-terminal amino acids of the isolated bFGF was in accordance with the established complete 146-amino-acid bFGF molecule except that glycine in position 10 is replaced by phenylalanine. An additionally identified minor peptide presumably is an amino-terminal-truncated form of bFGF, missing the first 15 amino acids. We conclude that the physiological significance of bFGF released by thyroid cells may be the regulation of angiogenesis during thyroid development and goiter growth.

A non-invasive evaluation of bone metabolism was performed in 44 morbidly obese patients before and after a mean weight loss of 22.4 kg (range 7.9-43.4 kg) after 2 months and a further weight loss of 7.3 kg after 8 months (0.8-20.0 kg). This weight reduction was obtained by a nutritionally adequate very-low-calorie diet. Before treatment the bone mineral content of the distal forearm was increased compared to normals (51.9 U vs. 43.7 U, p < 0.001). Bone formation was evaluated by serum alkaline phosphatase and serum osteocalcin. Serum alkaline phosphatase was increased (187.8 U/l vs 147.4 U/l, p < 0.001) while serum osteocalcin was lower than in the controls (0.67 nmol/l vs 0.98 nmol/l, p < 0.01). Bone resorption, as measured by the urinary hydroxyproline/creatinine ratio, was not increased in the obese patients (19.2 molar ratio x 10(-3) vs 16.7 molar ratio x 10(-3), NS). After 2 months, the bone mineral content had declined by 3.3%. Serum alkaline phosphatase remained unchanged (187.8 U/l vs 186.9 U/l, NS) but serum osteocalcin demonstrated a significant rise (3.94 nmol/l vs 10.53 nmol/l, p < 0.001), parallel to changes in the hydroxyproline/creatinine ratio (19.2 molar ratio x 10(-3) vs 25.2 molar ratio x 10(-3), p < 0.001). At 8 months, no further change in the bone mineral content was seen. The hydroxyproline/creatinine ratio did still increase (from 25.8 molar ratio x 10(-3) to 30.1 molar ratio x 10(-3), p < 0.05), while serum alkaline phosphatase and serum osteocalcin remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal Article Unusual presentation of a TSH-secreting pituitary adenoma Get access Paolo Beck-Peccoz Paolo Beck-Peccoz Institute of Endocrine Sciences, University of Milan, Italy Paolo Beck-Peccoz, Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore IRCCS, Via F. Sforza, 35, 20122-Milan, Italy Search for other works by this author on: Oxford Academic Google Scholar Acta Endocrinologica (Norway), Volume 129, Issue 4, Oct 1993, Page 283, https://doi.org/10.1530/acta.0.1290283 Published: 01 October 1993

A unique thyrotrophin (TSH)-secreting pituitary tumour is described in a patient with a history of recurrent thyrotoxicosis. Unlike other previously reported TSHomas, the tumour is insensitive to octreotide, a somatostatin analogue. It does not accumulate [111In]octreotide but expresses functional dopamine receptors and responds to the D-isomer of thyroxine, two characteristics beneficial in the management of the patient.

The claimed ability of non-steroidal antiandrogens to preserve libido and sexual potency is sought as a potential improvement in the palliative management of prostate cancer. A critical issue for the clinical use of these compounds is, however, the reported evidence in the rat of an excessive increase in testosterone concentrations as a consequence of the androgen negative feedback interruption. On the other hand, the recovery of testicular function after long-term inhibition by luteinizing hormone-releasing hormone (LHRH) analogs is also an important concern in view of the proposed use of these compounds for the treatment of several non-malignant conditions. We addressed these issues by studying the long-term endocrine effects induced by the administration of either the non-steroidal antiandrogen nilutamide or the depot preparation of D-Trp6-LHRH in men with prostate cancer. Treatment with the antiandrogen induced a marked increase in gonadotropin levels, LH concentrations rising from a mean (SEM) of 17.5 +/- 1.6 to a maximum of 56.6 +/- 6.9 kU/l (p < 0.001), while mean testosterone and 17 beta estradiol-concentrations rose only by about 50% and 70% over pretreatment values, testosterone levels reaching a plateau after 1 month of treatment. In the subjects treated with the LHRH agonist, 6 months after discontinuation of long-term administration the mean (+/- SEM) LH had risen to 36.9 +/- 6.8 IU/l while mean testosterone levels were still as low as 1.7 +/- 0.7 and rose only to a maximum of 4.2 +/- 1 nmol/l after high-dose human chorionic gonadotropin loadings.(ABSTRACT TRUNCATED AT 250 WORDS)

Five intact and four thyroparathyroidectomized (TPTX) lactating dairy cows were fitted with polyvinyl catheters implanted into the left carotid artery and the left mammary vein (for blood sampling) and into the right external jugular vein (for injections), and with a Foley catheter inserted into the urinary bladder. In these nine cows, daily morning and evening milking induced a prompt and transient rise in mammary venous blood plasma parathyroid hormone-related peptide (PTHrP)(1-34) concentrations, followed by an increase in both urinary phosphate concentration and phosphate renal clearance. Such a milking-induced phosphaturia was not observed when (tyr)34-bPTH(7-34)-NH2 (5 pmol/kg body wt) was infused during milking into the TPTX cows. These results indicate that PTHrP released systematically by the mammary gland during milking might be responsible for the observed phosphaturia.