Disease relevance of Prolactinoma

• In contrast to macroprolactinomas, other functioning pituitary tumors (GH-, TSH-, and ACTH-secreting) rarely shrink during dopamine agonist therapy, although the number of tumors studied is small [1].
• A prolactinoma was removed from a nulliparous woman who had acromegaly, galactorrhea-amenorrhea, elevated serum growth hormone and prolactin, and hypogonadotropinism [2].
• An autosomal dominant syndrome of prolactinomas, carcinoids, and hyperparathyroidism was described in four Newfoundland kindreds in 1980 and in one kindred from the Pacific Northwest in 1983 [3].
• To ascertain the mechanisms of bromocriptine in lowering serum prolactin (PRL) levels and reducing the cell size of human prolactinomas, stereological analysis at electron microscope level was performed on six adenomas treated with bromocriptine (10 mg/day for 2 weeks) and four untreated adenomas [4].
• Hyperprolactinemia and prolactinomas are among the abnormalities reported for women exposed prenatally to diethylstilbestrol (DES) [5].

Psychiatry related information on Prolactinoma

• Two eating disorder patients with hyperprolactinemia, attributed in the first to a prolactin-secreting pituitary macroadenoma and in the second to a microprolactinoma, are described [6].
• We describe a woman, suffering from Bipolar Disorder-manic episode, who exhibited prolactinoma while on risperidone therapy [7].
• In conclusion, the treatment with CV 205-502 normalizing PRL levels improves gonadal and sexual function and fertility in males with prolactinoma, providing good tolerability and excellent patient compliance to medical treatment [8].
• In patient B the prolactinoma was removed by surgery, in view of the serious nature of the psychotic disorder, to avoid psychotic relapse by treatment with a dopamine agonist [9].
• The authors report the case of a woman with borderline personality disorder who developed a prolactinoma probably induced by amisulpride [10].

High impact information on Prolactinoma

• Improvement in headache associated with prolactinoma during treatment with a somatostatin analogue: an "N of 1" study [11].
• To evaluate the long-term effects of dopamine agonists in the treatment of macroprolactinoma, we studied prolactin levels and tumor size for 30 to 88 months (57 +/- 14, mean +/- S.D.) in 38 patients treated with bromocriptine or lisuride [12].
• We conclude that dopamine agonists are usually effective treatments for macroprolactinoma and that after a response has been obtained, it can be maintained in many patients with a greatly reduced dose [12].
• CSF rhinorrhea after bromocriptine for prolactinoma [13].
• Old female rats with spontaneous prolactin-secreting pituitary tumors (prolactinomas) and young females with prolactinomas produced by prolonged estrogen treatment had damaged tuberoinfundibular dopaminergic neurons [14].

Chemical compound and disease context of Prolactinoma

• We have shown previously that human prolactinomas express transforming sequences of the heparin-binding secretory transforming gene (hst) which encodes fibroblast growth factor-4 (FGF-4) [15].
• In these patients the pre-operative diagnosis prolactinoma in these patients was made by demonstrating loss of the normal circadian prolactin profile and impaired prolactin response to intravenous thyrotrophin-releasing hormone (T.R.H.) and metoclopramide stimulation [16].
• Heterogeneity of prolactin responses to oestradiol benzoate in women with prolactinomas [17].
• Reexpression of p8 contributes to tumorigenic properties of pituitary cells and appears in a subset of prolactinomas in transgenic mice that hypersecrete luteinizing hormone [18].
• Three sequential contrast-enhanced direct coronal computed tomographic scans obtained over a four-year period failed to demonstrate any evidence of growth of the 5 mm microprolactinoma [19].

Biological context of Prolactinoma

• By dual-color interphase fluorescence in situ hybridization analysis using HMGA2-specific PACs and BACs, we found that the HMGA2 locus was amplified in seven of the eight prolactinoma samples examined [20].
• Receptor autoradiography showed PACAP types I and II binding sites in all groups of pituitary adenomas, except prolactinomas [21].
• In conclusion, the present work reports that a NGF-mediated autocrine loop with an inhibitory role in the control of cell proliferation and tumor progression is active in the more differentiated DA-sensitive prolactinoma cell lines and is lost in the most malignant prolactinoma cells refractory to the dopaminergic therapy [22].
• Together, these data suggest that maintenance of the transformed phenotype of pituitary GH3 cells requires expression of p8 and that it may play a similar role when reexpressed in a subset of lactotropes that form prolactinomas in vivo [18].
• These data indicate that in prolactinoma cells the effect of NGF on D(2) receptor expression is mediated by p75(NGFR) in a trkA-independent way and that NGF stimulation of p75(NGFR) activates NF-kappaB, which is required for D(2) gene expression [23].

Anatomical context of Prolactinoma

• A new human cell line was established from a prolactin (PRL) secreting pituitary adenoma [24].
• MMP-9 expression did not differ between noninvasive tumors and normal pituitary gland, or between different sized prolactinomas [25].
• The IgG fraction of MEN-1 prolactinoma plasma had far more activity in endothelial cells than did optimal concentrations of known growth factors or conditioned medium from prolactinoma cells [26].
• Outcome of cabergoline treatment in men with prolactinoma: effects of a 24-month treatment on prolactin levels, tumor mass, recovery of pituitary function, and semen analysis [27].
• One hundred and twelve surgically removed pituitary adenomas (30 GH-secreting, 25 prolactinomas, 15 ACTH-secreting, and 42 nonfunctioning tumors) were compared with 13 specimens of normal anterior pituitary gland [28].

Gene context of Prolactinoma

• Such compounds are thus candidates to counteract the undesired actions of PRL, not only in tumors, but also in dopamine-resistant prolactinomas [29].
• In contrast, SSTR2-selective analogues did not suppress PRL release from six cultured prolactinomas studied [30].
• However, new SSTR5-selective analogues suppressed in vitro PRL secretion (30-40%; P < 0.05) in four of six prolactinomas [30].
• Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms [31].
• BMP-4 is overexpressed in other prolactinoma models, including estradiol-induced rat prolactinomas and human prolactinomas, compared with normal tissue and other pituitary adenoma types (Western blot analysis of 48 tumors) [32].

Analytical, diagnostic and therapeutic context of Prolactinoma

• Serum prolactin concentrations were measured for 72 h after intramuscular injection of 1 mg of oestradiol benzoate in six normoprolactinaemic women and nineteen with a prolactinoma (eleven with an obviously enlarged pituitary fossa and eight with a normal pituitary fossa) [17].
• These results indicate that in situ dopamine enhancement gene therapy can be a useful tool for the treatment of prolactinoma [33].
• Oral administration of bromocriptine (5 mg), on the other hand, consistently decreased serum alpha-subunit and PRL levels in 2 patients with prolactinoma and alpha-subunit and GH levels in 1 acromegalic patient [34].
• Recently, it was demonstrated that somatostatin analogs preferential for the SSTR5 subtype suppress PRL release from prolactinoma cell cultures by 30-40% [35].
• Using RT-PCR analysis of total RNA from 38 human pituitary adenomas, we found that ER beta messenger RNA was coexpressed with ER alpha and its splice variants in 60% of prolactinomas, 100% of mixed GH/PRL tumors, and 29% of gonadotroph tumors [36].

References