Home About us Contact
|
Home About us Contact | ||
|
|
||
Gland Development (gland + development)
Kinds of Gland Development Selected AbstractsIdentification of Tgf,1i4 as a downstream target of Foxc1DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 5 2006Paula Sommer Craniofacial development is severely affected by null mutations in Foxc1, indicating a multifunctional role for Foxc1 in ocular, maxilla and mandible, skull and facial gland development. To delineate signaling pathways in which Foxc1 is involved we compared the transcriptomes of whole heads of Foxc1+/+ and Foxc1,/, embryos using a candidate cDNA array comprising genes expressed in the head mesenchyme and ocular region, and a 7K oligo array. Absence of Foxc1 led to downregulation of Stat1 and Galnt4, and upregulation of Tgf,1i4 at embryonic day 13.5 in the developing head mesenchyme. Comparative analyses revealed differences in the expression pattern of Tgf,1i4 in the head mesenchyme of Foxc1,/, and Foxc1+/+ embryos. In the ocular regions of Foxc1,/, embryos, Tgf,1i4 was expressed in higher levels in the conjunctival epithelium and in the condensing mesenchyme on the nasal aspect of the developing eye while in wild-type embryos more intense expression was seen in the mesenchyme on the temporal aspect of the eye. Such data indicate that Foxc1 regulation of Tgf,1i4 is complex and may be cell-type dependent. Analysis of the regulation of Tgf,1i4 by Foxc1 in a more homogenous cell population, mesenchymal cells isolated from the periocular region revealed that, in these cells, Foxc1 negatively regulated Tgf,1i4 expression, presumably via secreted factors such as TGF-,1. Since Foxc1 expression is essential for normal craniofacial development, it is possible that its downstream targets play a role in the development of the phenotypes associated with null mutations in Foxc1. [source] Impaired lactation in mice expressing dominant-negative FADD in mammary epitheliumDEVELOPMENTAL DYNAMICS, Issue 4 2009Mark Shackleton Abstract The Fas-associated death domain (FADD/Mort1) adaptor protein was originally identified as a key mediator of apoptosis, although pleiotropic functions for FADD have also been reported. FADD-mediated tumoricidal effects have been described in breast cancer cells; however, its physiological role in normal mammary gland epithelium is not well understood. To determine the role of FADD signaling during mammary gland development, we generated transgenic mice overexpressing dominant-negative FADD (DN-FADD) in mammary epithelium, using the steroid responsive mouse mammary tumor virus promoter. Transgenic mice exhibited a perturbation in lactation resulting in impaired milk production and pup growth retardation. Reduced expansion of alveoli was evident during early lactation with extensive shedding of luminal alveolar cells. Significantly more TUNEL (terminal deoxynucleotidyl transferase,mediated deoxyuridinetriphosphate nick end-labeling)-positive cells were present at this time point and a subsequent increase in bromodeoxyuridine-positive cells was observed. These findings suggest a role for FADD in maintaining the survival of mammary secretory alveolar cells after the establishment of lactation. Developmental Dynamics 238:1010,1016, 2009. © 2009 Wiley-Liss, Inc. [source] Role for notch signaling in salivary acinar cell growth and differentiationDEVELOPMENTAL DYNAMICS, Issue 3 2009Howard Dang Abstract The Notch pathway is crucial for stem/progenitor cell maintenance, growth and differentiation in a variety of tissues. The Notch signaling is essential for Drosophila salivary gland development but its role in mammalian salivary gland remains unclear. The human salivary epithelial cell line, HSG, was studied to determine the role of Notch signaling in salivary epithelial cell differentiation. HSG expressed Notch 1 to 4, and the Notch ligands Jagged 1 and 2 and Delta 1. Treatment of HSG cells with inhibitors of ,-secretase, which is required for Notch cleavage and activation, blocked vimentin and cystatin S expression, an indicator of HSG differentiation. HSG differentiation was also associated with Notch downstream signal Hes-1 expression, and Hes-1 expression was inhibited by ,-secretase inhibitors. siRNA corresponding to Notch 1 to 4 was used to show that silencing of all four Notch receptors was required to inhibit HSG differentiation. Normal human submandibular gland expressed Notch 1 to 4, Jagged 1 and 2, and Delta 1, with nuclear localization indicating Notch signaling in vivo. Hes-1 was also expressed in the human tissue, with staining predominantly in the ductal cells. In salivary tissue from rats undergoing and recovering from ductal obstruction, we found that Notch receptors and ligands were expressed in the nucleus of the regenerating epithelial cells. Taken together, these data suggest that Notch signaling is critical for normal salivary gland cell growth and differentiation. Developmental Dynamics 238:724,731, 2009. © 2009 Wiley-Liss, Inc. [source] Role for primary cilia in the regulation of mouse ovarian functionDEVELOPMENTAL DYNAMICS, Issue 8 2008Ellen T. Johnson Abstract Ift88 is a component of the intraflagellar transport complex required for formation and maintenance of cilia. Disruption of Ift88 results in depletion of cilia. The goal of the current study was to determine the role of primary cilia in ovarian function. Deletion of Ift88 in ovary using Cre-Lox recombination in mice resulted in a severe delay in mammary gland development including lack of terminal end bud structures, alterations in the estrous cycle, and impaired ovulation. Because estrogen drives the formation of end buds and Cre was expressed in the granulosa cells of the ovary, we tested the hypothesis that addition of estradiol to the mutant mice would compensate for defects in ovarian function and rescue the mammary gland phenotype. Mammary gland development including the formation of end bud structures resumed in mutant mice that were injected with estradiol. Together the results suggest that cilia are required for ovarian function. Developmental Dynamics 237:2053,2060, 2008. © 2008 Wiley-Liss, Inc. [source] Circadian clock and cell cycle gene expression in mouse mammary epithelial cells and in the developing mouse mammary glandDEVELOPMENTAL DYNAMICS, Issue 1 2006Richard P. Metz Abstract Mouse mammary epithelial cells (HC-11) and mammary tissues were analyzed for developmental changes in circadian clock, cellular proliferation, and differentiation marker genes. Expression of the clock genes Per1 and Bmal1 were elevated in differentiated HC-11 cells, whereas Per2 mRNA levels were higher in undifferentiated cells. This differentiation-dependent profile of clock gene expression was consistent with that observed in mouse mammary glands, as Per1 and Bmal1 mRNA levels were elevated in late pregnant and lactating mammary tissues, whereas Per2 expression was higher in proliferating virgin and early pregnant glands. In both HC-11 cells and mammary glands, elevated Per2 expression was positively correlated with c-Myc and Cyclin D1 mRNA levels, whereas Per1 and Bmal1 expression changed in conjunction with ,- casein mRNA levels. Interestingly, developmental stage had differential effects on rhythms of clock gene expression in the mammary gland. These data suggest that circadian clock genes may play a role in mouse mammary gland development and differentiation. Developmental Dynamics 235:263,271, 2006. © 2005 Wiley-Liss, Inc. [source] Retinoic acid signaling is required for proper morphogenesis of mammary glandDEVELOPMENTAL DYNAMICS, Issue 4 2005Y. Alan Wang Abstract Retinoic acid (RA), a bioactive chemical compound synthesized from dietary derived vitamin A, has been successfully used as a chemopreventive and chemotherapeutic agent through the regulation of cell proliferation, differentiation, and apoptosis acting via the retinoic acid receptors. Despite two decades of research on the function of retinoic acid, the physiological role of RA in mammary gland development is still not well characterized. In this report, we demonstrate that RA is required for proper morphogenesis of mouse mammary gland in a novel transgenic mouse model system. It was found that inhibition of RA signaling in vivo leads to excessive mammary ductal morphogenesis through upregulation of cyclin D1 and MMP-3 expression. Furthermore, we show that the transgene-induced excessive branching morphogenesis could be reversed by treatment with RA, demonstrating the direct physiological effect of RA signaling in vivo. In addition, we demonstrate that excessive branching morphogenesis in the transgenic mammary gland are cell-autonomous and do not require stromal signals within the transgenic mammary gland. Finally, we provide evidence suggesting that retinoic acid signaling is required for appropriate mammary gland differentiation. Collectively, our data indicate for the first time that retinoic acid signaling is required to maintain the homeostasis of mammary gland morphogenesis. Developmental Dynamics 234:892,899, 2005. © 2005 Wiley-Liss, Inc. [source] Post natal oestrogen administration stimulates precocious endometrial gland development in the horseEQUINE VETERINARY JOURNAL, Issue 7 2009S. WILSHER Summary Reasons for performing study: Fillies completely devoid of endometrial glands (uterine gland knockout; UGKO) would make ideal experimental models in which to study the role of endometrial histotroph in embryogenesis and early fetal development in the mare. Hypothesis: Administration of a synthetic progestagen plus oestrogen to newborn filly foals and, thereafter, at regular intervals to age 6 months, would permanently suppress endometrial gland development. Methods: Nine half-sister Thoroughbred filly foals were treated, in 3 groups, with: A) the weakly active progestagen, norgestomet, administered from birth to age 6 months, in subcutaneous implant form plus oestradiol valerate and norgestomet i.m. at fortnightly intervals; B) the strongly active oral progestagen, altrenogest, administered daily from birth to age 6 months plus fortnightly injections of oestradiol valerate and norgestomet; C) nothing (untreated controls). Endometrial biopsies were recovered from all fillies at ages 6 months and 2 years to assess the degree of endometrial gland morphogenesis and to determine immunohistochemically the presence or absence of oestrogen and progesterone receptors in the endometrial tissues. Results: Groups B and C showed no endometrial gland development, whereas Group A fillies showed a high degree of endometrial gland development, plus strong staining for both oestrogen and progesterone receptors at age 6 months. All 9 fillies showed full normal endometrial gland morphogenesis, development and function at age 2 years. Conclusions and relevance: While the administration of a strongly active progestagen over-rode the actions of the concomitantly administered oestrogen and suppressed endometrial gland development during the period of administration, treatment with oestradiol valerate together with a weakly active progestagen, stimulated precocious endometrial gland development. Neither steroid was able to create the desired UGKO experimental model and all fillies showed normal endometrial gland development and fertility after puberty. Hence, ovarian oestrogen, not progesterone, appears to be the basic stimulus for endometrial gland morphogenesis in the horse. [source] Aquaporin 11 in the developing mouse submandibular glandEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 1 2010Helga S. Larsen Larsen HS, Ruus A-K, Schreurs O, Kanli Galtung H. Aquaporin 11 in the developing mouse submandibular gland. Eur J Oral Sci 2010; 118: 9,13. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci Several aquaporins (AQPs) have been detected in mature and embryonic mammalian salivary glands (AQP1 and AQP3,AQP8). However, AQP11 has, to our knowledge, never before been described in salivary glands, but is known to be important in, for example, kidney development in mice. We therefore thought it relevant to investigate if AQP11 was present during salivary organogenesis. The submandibular salivary gland (SMG) from CD1 mice was studied during prenatal development and early postnatal development, and also in young adult male and female mice. The expression trend of the AQP11 transcript was detected using the reverse transcription,polymerase chain reaction (RT-PCR), and the temporal,spatial pattern was observed using in situ hybridization. The AQP11 transcript was first detected at embryonic day 13.5 and showed a more or less constitutive expression trend during the prenatal and early postnatal SMG development. Spatial studies demonstrated that the AQP11 transcript was present in the developing and mature duct structures at all stages studied. In the end pieces, the AQP11 transcript was reduced during glandular development. Our results point to an important role for AQP11 during salivary gland development. [source] Immunoexpression of extracellular matrix proteins in human salivary gland developmentEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 6 2004Cristiane Furuse Immunoexpression of the extracellular matrix (ECM) proteins laminin, fibronectin, tenascin and types I, III and IV collagen was analyzed in the major and minor salivary glands of seven human fetuses at different gestational ages. The results showed the presence and localization of laminin, collagen IV and fibronectin around glandular structures at all stages of development. Tenascin was only detectable around excretory ducts. In the earliest stages of development, type I and type III collagen were presented as fine fibers delineating the glandular structures and delimiting the extension of the future lobule. As glandular development proceeded, the lobule was gradually filled with collagens and glandular tissue. [source] PPFIA1 and CCND1 are frequently coamplified in breast cancerGENES, CHROMOSOMES AND CANCER, Issue 1 2010Ana-Maria Dancau Recently, amplification of PPFIA1, encoding a member of the liprin family located about 600 kb telomeric to CCND1 on chromosome band 11q13, was described in squamous cell carcinoma of head and neck. Because 11q13 amplification is frequent in breast cancer, and PPFIA1 has been suggested to contribute to mammary gland development, we hypothesized that PPFIA1 might also be involved in the 11q13 amplicon in breast cancer and contribute to breast cancer development. A tissue microarray containing more than 2000 human breast cancers was analyzed for gene copy numbers of PPFIA1 and CCND1 by means of fluorescence in situ hybridization. PPFIA1 amplification was found in 248/1583 (15.4%) of breast cancers. Coamplification with CCND1 was found in all (248/248, 100%) PPFIA1 -amplified cancers. CCND1 amplification without PPFIA1 coamplification was found in additional 117 (4.7%) tumors. Amplification of both PPFIA1 and CCND1 were significantly associated with high-grade phenotype (P = 0.0002) but were unrelated to tumor stage (P = 0.7066) or nodal stage (P = 0.5807). No difference in patient prognosis was found between 248 CCND1/PPFIA1 coamplified tumors and 117 tumors with CCND1 amplification alone (P = 0.6419). These data show that PPFIA1 amplification occurs frequently in breast cancer. The higher incidence of CCND1 amplification when compared with PPFIA1, the lack of prognostic relevance of coamplifications, and the fact that PPFIA1 amplification was found exclusively in CCND1 -amplified cancers suggest that PPFIA1 gene copy number changes represent concurrent events of CCND1 amplification rather than specific biological incidents. © 2009 Wiley-Liss, Inc. [source] Advances in sebaceous gland research: potential new approaches to acne managementINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 6 2004M. M. T. Downie Synopsis Sebaceous gland development and function is regulated by an expanding array of molecules including transcription factors, hormones, retinoids, growth factors, cytokines and nuclear hormone receptors. We have reviewed the literature to present the current understanding of sebaceous gland development and physiology, with particular emphasis on the control of the sebaceous gland and its implications for acne management. Interestingly, retinoids, cytokines and nuclear hormone receptors appear to be promising inhibitors of sebum synthesis, thus offering new approaches to acne management. Résumé Le développement et la fonction de la glande sébacée sont régulés par un grand nombre de molécules dont des facteurs de transcription, des hormones, des rétinoïdes, des facteurs de croissance, des cytokines et des récepteurs hormonaux nucléaires. Nous avons étudié la littérature pour présenter les dernières connaissances sur le développement et la physiologie de cet organe en insistant sur les facteurs les contrôlant et leurs implications sur le traitement de l'acné. De façon intéressante, des rétinoïdes, des cytokines, des récepteurs hormonaux nucléaires se montrent des inhibiteurs de synthèse du sébum prometteurs offrant de nouvelles approches pour le traitement de l'acné. [source] Interactions between FGF and Wnt signals and Tbx3 gene expression in mammary gland initiation in mouse embryosJOURNAL OF ANATOMY, Issue 1 2004Maxwell C. Eblaghie Abstract Interactions between Wnts, Fgfs and Tbx genes are involved in limb initiation and the same gene families have been implicated in mammary gland development. Here we explore how these genes act together in mammary gland initiation. We compared expression of Tbx3, the gene associated with the human condition ulnar,mammary syndrome, expression of the gene encoding the dual-specificity MAPK phosphatase Pyst1/MKP3, which is an early response to FGFR1 signalling (as judged by sensitivity to the SU5402 inhibitor), and expression of Lef1, encoding a transcription factor mediating Wnt signalling and the earliest gene so far known to be expressed in mammary gland development. We found that Tbx3 is expressed earlier than Lef1 and that Pyst1 is also expressed early but only transiently. Patterns of expression of Tbx3, Pyst1 and Lef1 in different glands suggest that the order of mammary gland initiation is 3, 4, 1, 2 and 5. Consistent with expression of Pyst1 in the mammary gland, we detected expression of Fgfr1b, Fgf8 and Fgf9 in both surface ectoderm and mammary bud epithelium, and Fgf4 and Fgf17 in mammary bud epithelium. Beads soaked in FGF-8 applied to the flank of mouse embryos, at a stage just prior to mammary bud initiation, induce expression of Pyst1 and Lef1 and maintain Tbx3 expression in flank tissue surrounding the bead. Grafting beads soaked in the FGFR1 inhibitor, SU5402, abolishes Tbx3, Pyst1 and Lef1 expression, supporting the idea that FGFR1 signalling is required for early mammary gland initiation. We also showed that blocking Wnt signalling abolishes Tbx3 expression but not Pyst1 expression. These data, taken together with previous findings, suggest a model in which Tbx3 expression is induced and maintained in early gland initiation by both Wnt and Fgf signalling through FGFR1. [source] TGF-, inhibits prolactin-induced expression of ,-casein by a Smad3-dependent mechanism,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2008Wen-Jun Wu Abstract Transforming growth factor-, (TGF-,) is a multifunctional growth factor, affecting cell proliferation, apoptosis, and extracellular matrix homeostasis. It also plays critical roles in mammary gland development, one of which involves inhibition of the expression of milk proteins, such as ,-casein, during pregnancy. Here we further explore the underlying signaling mechanism for it. Our results show that TGF-, suppresses prolactin-induced expression of ,-casein mRNA and protein in primary mouse mammary epithelial cells, but its effect on protein expression is more evident. We also find out that this inhibition is not due to the effect of TGF-, on cell apoptosis. Furthermore, inhibition of TGF-, type I receptor kinase activity by a pharmacological inhibitor SB431542 or overexpression of dominant negative Smad3 substantially restores ,-casein expression. By contrast, inhibition of p38 and Erk that are known to be activated by TGF-, does not alleviate the inhibitory effect of TGF-,. These results are consistent with our other observation that Smad but not MAPK pathway is activated by TGF-, in mammary epithelial cells. Lastly, we show that prolactin-induced tyrosine phosphorylation of Jak2 and Stat5 as well as serine/threonine phosphorylation of p70S6K and S6 ribosomal protein are downregulated by TGF-,, although the former event requires considerably long exposure to TGF-,. We speculate that these events might be involved in repressing transcription and translation of ,-casein gene, respectively. Taken together, our results demonstrate that TGF-, abrogates prolactin-stimulated ,-casein gene expression in mammary epithelial cells through, at least in part, a Smad3-dependent mechanism. J. Cell. Biochem. 104: 1647,1659, 2008. © 2008 Wiley-Liss, Inc. [source] Primary adrenal insufficiency in childhood and adolescence: Advances in diagnosis and managementJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 11 2004PJ Simm Objectives: Primary adrenal insufficiency occurring in childhood and adolescence is due to abnormalities of gland development, gland responsiveness, and steroid biosynthesis or target organ response. Causes include autoimmune Addison's disease, tuberculosis, HIV, adrenoleukodystrophy, adrenal hypoplasia congenita and syndromes including triple A and IMAGe. We aimed to define the causes of adrenal insufficiency for a cohort of children in Melbourne. Methods: We reviewed the frequency and variety of presentation of primary adrenal insufficiency to the Royal Children's Hospital over the past 10 years through an audit of patient records, collating demographic information, presentation and investigations. Results: Sixteen cases (13 male, 3 female) of primary adrenal insufficiency were diagnosed at this hospital between January 1993 and July 2003. Median age at presentation was 7.7 years (range: birth to 14.8 years). Symptoms at presentation included weakness, increased pigmentation, abdominal pain, nausea, developmental delay or a reduction in school performance. Four patients presented with adrenal crisis. Median adrenocorticotrophic hormone (ACTH) at diagnosis was 246 pmol/L (range 30,969 pmol/L). Autoantibodies were positive in five patients. Five patients had elevation of very long chain fatty acids. Five patients were diagnosed with autoimmune adrenal insufficiency, five with adrenal hypoplasia congenita, five with adrenoleukodystrophy and one with IMAGe syndrome. Conclusions: A high index of suspicion results in earlier detection and possible prevention of adrenal crisis with a reduction in associated morbidities. Definitive diagnosis is now possible for almost all cases of primary adrenal insufficiency using technologies for screening autoimmunity, adrenoleukodystrophy (ALD) and genetic screening. [source] Atypical Fetal Prostate Development is Associated with Ipsilateral Hypoplasia of the Wolffian Ducts in the ACI RatTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 5 2010Luke E. Hofkamp Serial section reconstruction images of the male ACI rat urogenital sinus shown from a dorso-cranial view. The image in the lower right illustrates the normal late gestation appearance of the accessory gland development, compared to the Wolffian duct ipsilateral abnormality observed in 25% of the male offspring (upper left). See Potok et al., Anatomical Record 239:747,753. [source] Hepatocyte Growth Factor Receptor, c-Met, in Human Embryo Salivary Glands.ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 3 2010An Immunohistochemical Study With 3 figures and 1 table Summary Salivary gland morphogenesis involves complex, coordinated events that include epithelial,mesenchymal interactions. Mesenchymal,epithelial transition factor (c-Met) is the hepatocyte growth factor (HGF) receptor. The latter is a hepatotropic factor originally identified in rat serum and platelets. It is essential in fetal tissue development, where it regulates complex morphogenetic processes including extracellular matrix invasion, cell migration, cell polarization and tubulogenesis. The c-Met/HGF system is believed to participate in epithelial,mesenchymal interactions during development. Twelve human embryonic minor salivary glands were studied by immunohistochemistry to investigate the role of c-Met in human salivary gland development. Strong c-Met immunopositivity in the glands demonstrated that the molecule is involved in their development and suggested a role for the c-Met/HGF system in this process. [source] Database of cattle candidate genes and genetic markers for milk production and mastitisANIMAL GENETICS, Issue 6 2009J. Ogorevc Summary A cattle database of candidate genes and genetic markers for milk production and mastitis has been developed to provide an integrated research tool incorporating different types of information supporting a genomic approach to study lactation, udder development and health. The database contains 943 genes and genetic markers involved in mammary gland development and function, representing candidates for further functional studies. The candidate loci were drawn on a genetic map to reveal positional overlaps. For identification of candidate loci, data from seven different research approaches were exploited: (i) gene knockouts or transgenes in mice that result in specific phenotypes associated with mammary gland (143 loci); (ii) cattle QTL for milk production (344) and mastitis related traits (71); (iii) loci with sequence variations that show specific allele-phenotype interactions associated with milk production (24) or mastitis (10) in cattle; (iv) genes with expression profiles associated with milk production (207) or mastitis (107) in cattle or mouse; (v) cattle milk protein genes that exist in different genetic variants (9); (vi) miRNAs expressed in bovine mammary gland (32) and (vii) epigenetically regulated cattle genes associated with mammary gland function (1). Fourty-four genes found by multiple independent analyses were suggested as the most promising candidates and were further in silico analysed for expression levels in lactating mammary gland, genetic variability and top biological functions in functional networks. A miRNA target search for mammary gland expressed miRNAs identified 359 putative binding sites in 3,UTRs of candidate genes. [source] Application of new homologous in vitro bioassays for human lactogens to assess the actual bioactivity of human prolactin isoforms in hyperprolactinaemic patientsCLINICAL ENDOCRINOLOGY, Issue 2 2006Alfredo Leaños-Miranda Summary Background, ,Prolactin (PRL) plays a central role in mammary gland development and lactation. Due to its molecular heterogeneity, measurement of PRL immunoreactivity does not necessarily reflect its intrinsic bioactivity. For many years the Nb2 rat lymphoma cell bioassay has been the only reference bioassay for human lactogens. This bioassay, however, does not always correlate with the clinical features found in some patients exhibiting normal or elevated immunoreactive serum PRL concentrations. Objectives, ,(1) To determine the concentrations of bioactive PRL in serum samples from individuals with normoprolactinaemia or with different forms of hyperprolactinaemia using two recently described homologous in vitro bioassays (i.e. a transcriptional bioassay in HEK-293 cells and a proliferation assay in Ba/F3 cells); and (2) to compare these results with those generated by the classical Nb2 cell bioassay. Design, ,Cross-sectional study. Setting, ,An institutional biomedical research laboratory. Participants, ,Ten patients with symptomatic hyperprolactinaemia due to prolactinoma, 11 patients with asymptomatic hyperprolactinaemia and macroprolactinaemia, and nine normal women. Main outcome measures, ,Measurement of immunoreactive and bioactive concentrations of serum PRL. Results, ,Samples from normal women and patients with tumoral hyperprolactinaemia due to prolactinoma exhibited similar within-group concentration values of bioactive and immunoreactive serum PRL when tested by the three bioassays and the immunoradiometric assay employed. By contrast, measurement of bioactive PRL in samples from patients with macroprolactinaemia revealed that macroprolactin was poorly active in the homologous receptor bioassays, while it was more active in the Nb2 bioassay. Conclusions, ,The reduced bioactivity of PRL in patients with macroprolactinaemia may further explain the absence of clinical features of hyperprolactinaemia in these individuals. In addition, our findings indicate that species-specificity and sensitivity of the bioassays are determinant factors in the measurement of the intrinsic biological activity of circulating PRL. [source] | |||||||||||||