Cysteamine: a Potent and Specific Depletor of Pituitary Prolactin

Wj, Millard; Sagar, S.M.; Landis, Dennis M.D.; Jb, Martin

doi:10.1126/science.7089575

Cited by 89 publications

(35 citation statements)

References 21 publications

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“…The plasma G H concentration was found to be markedly depressed in the rats with ARC lesions in the present study, similar to that found in rats with electrical or chemical lesions of the ARC in previous reports (1 5,19). CSH is known to be a depletor of SRIF and its reduction of SRIF levels in the hypothalamus is dose-dependent (16,20,21 (22,23). Indeed, serum levels of free T, were found to be decreased in the CSH-treated rats with ARC lesions.…”

Section: Discussionsupporting

confidence: 79%

Effects of Somatostatin on the Growth Hormone‐Releasing Factor‐Induced Growth Hormone Secretion in Rats with Electrical and Chemical Inhibitions of Endogenous Growth Hormone‐Releasing Factor and Somatostatin

Sato

Takahara

Niimi

et al. 1990

J Neuroendocrinology

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The episodic pattern of growth hormone (GH) secretion of the male rat was simulated in rats exhibiting impaired GH-releasing factor (GRF) and somatostatin (SRIF) secretion, by administering various combinations of human GRF-(1-44)NH2 (hGRF) and SRIF. Electrical lesions of the arcuate nucleus resulted in a marked decrease in the amplitude of GH secretory bursts, while the administration of cysteamine (200 mglkg) did not change the GH secretory profile in rats with arcuate nucleus lesions. lmmunohistochemical examinations revealed a marked decrease of GRF and SRlF immunoreactivity in the median eminence of the cysteamine-treated rats with arcuate nucleus lesions. The intravenous injection of 5 pg of hGRF every 3 h caused equivalent surges of GH in the cysteamine-treated rats with arcuate nucleus lesions. The additional infusion of 4 pglh of SRlF during the trough periods of GH secretion did not affect the amplitude of the GH surges. Hourly injection of 5 pg of hGRF caused transient desensitization to hGRF. Interestingly, the additional infusion of 4 pglh of SRlF every 3 h enhanced the amplitude of the GH bursts induced by the fourth and the seventh hGRF injections. However, the more frequent injection of 5 pg of hGRF every 30 min caused constant desensitization to hGRF with time, and the additional infusion of 4 pglh of SRlF every 3 h did not change the attenuated responses to hGRF. These results indicated that the simultaneous administration of hourly GRF and continuous SRlF with brief pauses was most effective for producing high GH peaks. This simulation model suggests that SRlF may play an important role not only in the production of GH troughs, but also in the maintenance of GH surges with distinct peaks in the male rat.

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Section: Discussionsupporting

confidence: 79%

Effects of Somatostatin on the Growth Hormone‐Releasing Factor‐Induced Growth Hormone Secretion in Rats with Electrical and Chemical Inhibitions of Endogenous Growth Hormone‐Releasing Factor and Somatostatin

Sato

Takahara

Niimi

et al. 1990

J Neuroendocrinology

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“…Cys teamine is a sulfhydryl drug which causes a rapid, revers ible and dose-dependent depletion of both pituitary and serum PRL levels [32], It does not act through interacting with DA receptors or increasing intracellular digestive processes of PRL [32]. Instead, it may disrupt the disul fide bridges within the PRL molecule and reduce the immunoreactivity of PRL [33].…”

Section: Discussionmentioning

confidence: 99%

Enhanced Tuberoinfundibular Dopaminergic Neuron Activity in Thyroidectomized, Ovariectomized and Estrogen-Treated Rats with Hyperprolactinemia

Yang

Pan²

1994

Neuroendocrinology

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The involvement of the tuberoinfundibular dopaminergic (TIDA) neurons in the genesis of hyperprolactinemia in female thyroidectomized rats treated with estrogen was the focus of this study. Rats that were ovariectomized (3 weeks), thyroidectomized (2 weeks) and treated with estrogen for 6 days had a 5- to 10-fold increase in serum prolactin (PRL) levels, while the rats receiving the same treatments but without estrogen had lower PRL levels. The activity of TIDA neurons, using dihydroxyphenylacetic acid (DOPAC) concentration or the DOPAC/dopamine (DA) ratio in the median eminence (ME) as an index, was increased and decreased in estrogen-treated and untreated rats, respectively. The increases in serum PRL level and the activity of TIDA neurons were dependent on the duration of thyroidectomy and could both be lowered by daily injection of thyroid hormone (20 or 100 µg/kg b.w. thyroxine, i.p.) for 12 days in a dose-dependent manner. Using dihydroxyphenylalanine (DOPA) accumulation in the ME as another index, we also found an increased DOPA/DA ratio in estrogen-treated hypothyroid rats, which effect could be reversed by replacement of thyroid hormone. Furthermore, treatments with bromocryptine (3 mg/kg b.w./day, s.c.) for 3 days or with cysteamine (100 mg/kg b.w., s.c.) at 26, 15 and 2 h before the rats were sacrificed lowered both serum PRL level and TIDA neuron activity. Since PRL can exert a short-loop feedback control on its own secretion, these results indicate that the increased serum PRL levels in estrogen-treated hypothyroid female rats should be the cause, but not the result, of the increased activity of TIDA neurons.

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“…Alternatively, either pantothenate or cysteamine could be responsible for pantethine's hypolipemic action. Cysteamine has numerous pharmacologic actions (21) and hormonal effects (47,48). Pantothenate deficiency has been reported to lower blood cholesterol levels in the rat (49) and dog (50), but this was not demonstrated in humans (51).…”

Section: Discussionmentioning

confidence: 99%

Metabolism of pantethine in cystinosis.

et al. 1985

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D-Pantethine is a conjugate of the vitamin pantothenic acid and the low-molecular-weight aminothiol cysteamine. Pantethine is an experimental hypolipemic agent and has been suggested as a source of cysteamine in the treatment of nephropathic cystinosis. We treated four cystinotic children with 70-1,000 mg/kg per d oral D-pantethine and studied its metabolism. Pantethine was rapidly hydrolyzed to pantothenic acid and cysteamine; we could not detect pantethine in plasma after oral administration. The responsible enzyme, "pantetheinase," was highly active in homogenates of small intestinal mucosa and plasma. The Michaelis constant of the rat intestinal enzyme was 4.6 MM and its pH profile showed a broad plateau between 4 and 9. Pantothenate pharmacokinetics after orally administered pantethine followed an open two-compartment model with slow vitamin elimination (t1/2 = 28 h). Peak plasma pantothenate occurred at 2.5 h and levels over 250 MM were seen at 300 times normal. Apparent total body storage of pantothenate was significant (25 mg/kg), and plasma levels were elevated threefold for months after pantethine therapy. Plasma cysteamine concentrations after pantethine were similar to those reported after equivalent doses of cysteamine. However, at best only 80% white blood cell cystine depletion occurred. We conclude that pantethine is probably less effective than cysteamine in the treatment of nephropathic cystinosis and should only be considered in cases of cysteamine intolerance. Serum cholesterol was decreased an average of 14%, which supports the potential clinical significance of pantethine as a hypolipemic agent. Rapid in vivo hydrolysis of pantethine suggests that pantothenate or cysteamine may be the effectors of its hypolipemic action.

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Cysteamine: a Potent and Specific Depletor of Pituitary Prolactin

Cited by 89 publications

References 21 publications

Effects of Somatostatin on the Growth Hormone‐Releasing Factor‐Induced Growth Hormone Secretion in Rats with Electrical and Chemical Inhibitions of Endogenous Growth Hormone‐Releasing Factor and Somatostatin

Effects of Somatostatin on the Growth Hormone‐Releasing Factor‐Induced Growth Hormone Secretion in Rats with Electrical and Chemical Inhibitions of Endogenous Growth Hormone‐Releasing Factor and Somatostatin

Enhanced Tuberoinfundibular Dopaminergic Neuron Activity in Thyroidectomized, Ovariectomized and Estrogen-Treated Rats with Hyperprolactinemia

Metabolism of pantethine in cystinosis.

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