Prolactin Receptor Gene Research Articles

MRNA expression, polymorphism of prolactin receptor gene and their association with prolificacy in Lezhi black goats

mRNA expression and DNA polymorphism of prolactin receptor (PRLR) gene were investigated and used to study their effects on litter size in goats. Real-time polymerase chain reaction (PCR) analysis revealed that PRLR mRNA levels in pituitary and endometrium of prolific Lezhi black goats were 39.0-fold and 29.9-fold higher than those in non-prolific Tibetan goats (P < 0.05), but there was no difference in ovary and liver between the two breeds. To further explore the possible association between variations in PRLR gene with litter size in Lezhi black goat, mutation screening of exon 10 of PRLR was performed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). In P2 locus, the four genotypes AA, AB, AC, and AD had the genotypic frequencies of 0.136, 0.110, 0.162, and 0.594, respectively, but no polymorphism was detected in P1 locus. There were four mutations at C89T, A94C, C146G, and G157C of this fragment in all of the four genotypes, which led to a missense mutation Pro to Leu, Asn to His, Ala to Gly, and Ala to Pro, respectively. In addition, a mutation of C61T in genotype AA, A175G in genotype AD, T24C and C96T in genotype CD were detected. The Lezhi black does with genotype AD had 0.35 (P < 0.05) more kids than those with genotype AB, but there was no significant difference among other genotypes. It is concluded that PRLR gene expression and mutations in exon 10 of PRLR gene may be associated with the reproductive effects of the Lezhi black goat.

Abstract P3-07-11: Nipple aspiration fluid yielders and non-yielders: Genetic characteristics

Abstract Background: Nipple aspiration fluid (NAF) is a noninvasively acquired biosample that can provide a window of observation into the breast environment, but NAF yield is variable across studies, and is related to a variety of demographic and reproductive factors. We have recently observed a positive correlation between serum prolactin level and NAF yield status. The genetic traits determining NAF yield are unknown, but data from the 1970s linked wet type ear wax to NAF yield, and recent studies point to single nucleotide polymorphisms (SNPs) in the ABCC11 gene as a determinant of earwax type. Further, prolactin and prolactin receptor SNPs are related to serum prolactin level. We have investigated associations between NAF yield and SNPs in prolactin, prolactin receptor and ABCC11 genes in a recently completed case-control study. Method: NAF and/or blood were collected from 916 women. Subjects were defined as yielder if NAF volume was equal or more than 2μL and non-yielder if it was less than 2μL. According to this definition, our subjects categorized as 557 yielders and 359 non-yielders. DNA was extracted from blood using Qiagen kit and 20 ng of DNA was used to amplify and genotype for ABCC11 (rs17822931), PRLR (rs37364), PRL (rs2244502), PRL (rs849872) SNPs using Taqman genotyping assay on an Applied Biosystems 7900HT machine. Results: The median age of Yielders and Non-yielders was 51 and 54, respectively, with the same range of 31-70 for both groups (P&amp;lt;0.0001). There were 209(38%) premenopausal, 257(46%) postmenopausal and 81(15%) perimenopausal of yielders vs. 99(28%) premenopausal, 229(64%) postmenopausal and 26(7%) perimenopausal of non-yielders (P&amp;lt;0.0001). ABCC11 genotype distribution was significantly different between yielders and non-yielders (P = 0.00163). However, genotype distribution was not significantly different for PRLR (rs37364), PRL (rs2244502) and PRL (rs849872). YNYTotalP (N vs. NY)ABCC11 (rs17822931)5413578980.00163CC437 (81%)269 (75%)706 TT5 (1%)16 (4%)21 CT99 (18%)72 (20%)171 PRLR (rs37364)5483599070.176GG89 (16%)43 (12%)132 TT272 (50%)181 (50%)453 GT187 (34%)135 (38%)322 PRL (rs2244502)5393588970.087AA73 (14%)32 (9%)105 TT233 (43%)155 (43%)388 AT233 (43%)171 (48%)404 PRL (rs849872)5433599020.102CC17 (3%)11 (3%)28 TT332 (61%)244 (68%)576 CT194 (36%)104 (29%)298 Conclusion: Our analysis demonstrates a correlation between ABCC11 (rs17822931) SNP and NAF yield status, with the major homozygous CC allele associated with NAF yielder and minor homozygous TT allele associated with non-yielder status. If NAF-based risk biomarkers are to be developed, a better understanding of the genetics of NAF yield is required. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-07-11.

Mutant Prolactin Receptor and Familial Hyperprolactinemia

Hyperprolactinemia that is not associated with gestation or the puerperium is usually due to tumors in the anterior pituitary gland and occurs occasionally in hereditary multiple endocrine neoplasia syndromes. Here, we report data from three sisters with hyperprolactinemia, two of whom presented with oligomenorrhea and one with infertility. These symptoms were not associated with pituitary tumors or multiple endocrine neoplasia but were due to a heterozygous mutation in the prolactin receptor gene, PRLR, resulting in an amino acid change from histidine to arginine at codon 188 (His188Arg). This substitution disrupted the high-affinity ligand-binding interface of the prolactin receptor, resulting in a loss of downstream signaling by Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5). Thus, the familial hyperprolactinemia appears to be due to a germline, loss-of-function mutation in PRLR, resulting in prolactin insensitivity.

Mutations in genes involved in oestrous cycle associated expression of oestrus

Detection of oestrus is a key determinant of profitability of dairy herds, but oestrus is increasingly difficult to observe in the modern dairy cow, with shorter duration and less intense oestrus. Concurrent with the unfavourable correlation between milk yield and fertility, oestrous detection rates have decreased to less than 50%. A number of mutations have been identified in genes associated with fertility and production traits, but, to date, no single nucleotide polymorphism (SNP) has been associated with oestrous expression. Therefore, the objective of this study was to investigate SNPs, linked to fertility, for the association with oestrous expression. Blood was collected from 205 Holstein Friesian dairy cows and genotyped at 41 loci of 18 genes chosen for their roles in the oestrous cycle and milk production. SNPs were then examined for correlations with increase in activity at oestrus, recorded via activity monitors, using generalised linear models. Physical activity increased at oestrus between two and four fold. Larger increases were associated with mutant alleles in oestrogen receptor-α and gonadotrophin releasing hormone receptor genes (P<0.05) and in the STAT5A gene (P<0.05). Smaller increases were associated with mutant alleles of the activin receptor type IIB and prolactin receptor genes (P<0.10). In conclusion, alleles in these five genes provide the opportunity for selection of animals displaying greater oestrous activity which could aid reversal of the decrease in oestrous detection and thereby contribute to sustainability of the dairy industry worldwide.

Sex-dependent roles of prolactin and prolactin receptor in postoperative pain and hyperalgesia in mice

Although surgical trauma activates the anterior pituitary gland and elicits an increase in prolactin (PRL) serum levels that can modulate nociceptive responses, the role of PRL and the PRL-receptor (PRL-R) in thermal and mechanical hyperalgesia in postoperative pain is unknown. Acute postoperative pain condition was generated with the use of the hindpaw plantar incision model. Results showed endogenous PRL levels were significantly increased in serum, operated hindpaw and spinal cords of male and female rats 24h after incision. These alterations were especially pronounced in females. We then examined the role of the PRL system in thermal and mechanical hyperalgesia in male and female mice 3–168h after plantar incision with the use of knock-out (KO) mice with PRL or PRL-R gene ablations and in wild-type (WT) mice. WT mice showed postoperative cold hyperalgesia in a sex-dependent manner (only in females), but with no effect on heat hyperalgesia or mechanical allodynia in either sex. Studies in KO mice showed no effect of PRL and PRL-R gene ablation on heat and cold hyperalgesia in male mice, while heat hyperlgesia were reduced 3–72h post-surgery in female PRL and PRL-R KO mice. In contrast, PRL and PRL-R ablations significantly attenuated mechanical allodynia 3–72h post-surgery in both male and female mice. Overall, we found elevated PRL levels in serum, hindpaws and spinal cords after incision, and identify a contributory role for the PRL system in postoperative pain responses to thermal stimuli in females and to mechanical stimuli in both males and females.

Combined effects of four SNPs within goat PRLR gene on milk production traits

Xinong Saanen (SN, n=323) and Guanzhong (GZ, n=197) goat breeds were used to detect single nucleotide polymorphisms (SNPs) in the coding regions with their intron–exon boundaries of prolactin receptor (PRLR) gene by DNA sequencing, primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Four novel SNPs (g.40452T>C, g.40471G>A, g.61677G>A and g.61865G>A) were identified. The g.61677G>A and g.61865G>A SNPs caused amino acid variations p.Ser485Asn and p.Val548Met, respectively. Both g.40452T>C and g.40471G>A loci were closely linked in SN and GZ goat breeds (r2>0.33). In addition, there was also a close linkage between g.61677G>A and g.61865G>A loci in both goat breeds. Statistical results indicated that the g.40452T>C, g.61677G>A and g.61865G>A SNPs were significantly associated with milk production traits in SN and GZ breeds. Further analysis revealed that combinative genotype C1 (TTAAGGGG) was better than the others for milk yield in SN and GZ goat breeds. These results are consistent with the regulatory function of PRLR in mammary gland development, milk secretion, and expression of milk protein genes, and extend the spectrum of genetic variation of the caprine PRLR gene, which might contribute to goat genetic resources and breeding.

Characterization of the novel duplicated PRLR gene at the late-feathering K locus in Lohmann chickens

A partial duplication of the prolactin (PRL) receptor gene (designated as dPRLR) has been identified at the late-feathering (LF) K locus on chromosome Z of some chicken strains recently, implying that dPRLR is probably a candidate gene associated with LF development in chickens. However, little is known about the structure, functionality, and spatiotemporal expression of the dPRLR gene in chickens. In this study, using 3'-RACE and RT-PCR, the full-length cDNA of the dPRLR obtained from the kidneys of male Lohmann layer chickens carrying a K allele was cloned. The cloned dPRLR is predicted to encode a membrane-spanning receptor of 683 amino acids, which is nearly identical to the original PRLR, except for its lack of a 149-amino acid C-terminal tail. Using a 5× STAT5-Luciferase reporter system and western blot analysis, we demonstrated that dPRLR expressed in HepG2 cells could be potently activated by chicken PRL and functionally coupled to the intracellular STAT5 signaling pathway, suggesting that dPRLR may function as a novel receptor for PRL. RT-PCR assays revealed that similar to the original PRLR gene, dPRLR mRNA is widely expressed in all embryonic and adult tissues examined including the skin of male Lohmann chickens with a K allele. These findings, together with the expression of PRL mRNA detected in the skin of embryos at embryonic day 20 and 1-week-old chicks, suggest that skin-expressed dPRLR and PRLR, together with plasma and skin-derived PRL, may be involved in the control of the LF development of chicks at hatching. Moreover, the wide tissue expression of dPRLR implies that dPRLR may regulate other physiological processes of chickens carrying the K allele.

Salinity changes in the anadromous river pufferfish, Takifugu obscurus, mediate gene regulation

This study aimed to better understand the hydromineral regulatory response of the anadromous river pufferfish, Takifugu obscurus, to salinity changes through real-time RT-PCR. After abrupt transfer from 30 or 5 psu to 5 or 30 psu, respectively, we analyzed the mRNA expression of Na⁺/K⁺ ATPase, prolactin receptor, and aquaporin from osmoregulatory organs of the river pufferfish such as gills, kidney, and intestine. Na⁺/K⁺ ATPase showed notable changes in the gills and kidney when salinity was increased. In the gills, the expression level of Na⁺/K⁺ ATPase suddenly increased within a day after abrupt transfer from 5 to 30 psu and then slightly declined within 2 days after exposure. In the kidney, Na⁺/K⁺ ATPase has shown consistently high mRNA expression after the increase in salinity. Expression levels of the prolactin receptor gene increased when environmental salinity decreased. In the intestine, gene expression of the prolactin receptor remained high, even when salinity decreased. To the contrary, there was a steady increase or decrease in mRNA expression in the kidney in response to salinity decrease or increase, respectively. As for aquaporins, aquaporin 1 was mainly expressed in the intestine and kidney, and aquaporin 3 was mainly expressed in the gills and intestine. In the gills, increased expression of aquaporin 3 was found after transfer to lower salinity and in the intestine and kidney, a decrease in salinity followed by an abrupt decrease in aquaporin 1 and aquaporin 3. Contrastingly, the expression of these genes increased in the intestine after transfer to 30 psu. Osmoregulatory genes were expressed in diverse organs, apparently to overcome an influx or exhaust of water or ions. A superior adaptation ability of the river pufferfish to a wide range of salinities is most reasonably due to active osmoregulatory processes mediated by the genes monitored here.

Prolactin Receptor Gene Polymorphisms Are Associated with Gestational Diabetes

Human placental lactogen (hPL) acts via the prolactin receptor (PRLR) on maternal β-cells to mediate increases in β-cell mass and function during normal pregnancy. This interaction between hPL and PRLR is essential to maintain normal glucose homeostasis and to address the increased metabolic demands of pregnancy. Given the importance of the PRLR-hPL axis in pancreatic islet cell adaptation to pregnancy, we hypothesized that genetic variation in the PRLR gene could influence risk of development of gestational diabetes mellitus (GDM). DNA samples from 96 mothers affected by GDM and 96 unaffected cases were genotyped for 8 selected single nucleotide polymorphisms (SNPs) in PRLR. Significant associations were identified in two SNPs analyzed. The minor alleles of PRLR SNPs rs10068521 and rs9292578 were more frequently observed in GDM cases than controls and were associated with a 2.36-fold increased risk for GDM in those carrying the minor allele. SNPs of the PRLR gene 5' UTR and promoter region are associated with increased risk for GDM in a population of Chilean subjects.

Novel polymorphisms detected in the prolactin receptor gene of Yili horse (&lt;i&gt;Equus caballus&lt;/i&gt;) by PCR-SSCP

Novel polymorphisms detected in the prolactin receptor gene of Yili horse (&lt;i&gt;Equus caballus&lt;/i&gt;) by PCR-SSCP

Molecular characterization of prolactin receptor (cPRLR) gene in chickens: Gene structure, tissue expression, promoter analysis, and its interaction with chicken prolactin (cPRL) and prolactin-like protein (cPRL-L)

In this study, gene structure, tissue expression, and promoter usage of prolactin receptor (PRLR) and its interaction with prolactin (PRL) and the newly identified prolactin-like protein (PRL-L) were investigated in chickens. The results showed that (1) PRLR gene was found to consist of at least 25 exons by 5′-RACE and RT-PCR assays; (2) multiple PRLR 5′-UTR sequences different in exon composition were isolated from chicken liver or intestine by 5′-RACE and could be subdivided into type I and type II transcripts according to the first exon used (exon 1G or exon 1A); (3) PRLR Type I transcripts with exon 1G were detected to be predominantly expressed in adult kidney and small intestine by RT-PCR, implying their expression is likely controlled by a tissue-specific promoter (P1). By contrast, PRLR type II transcripts containing exon 1A are widely expressed in adult and embryonic tissues examined and their expression is controlled by a generic promoter (P2) near exon 1A, which was demonstrated to display promoter activities in cultured DF-1, HEK293 and LoVo cells by the dual-luciferase reporter assay; (4) Using a 5×STAT5-luciferase reporter system, cPRLR expressed in HepG2 cells was shown to be activated by recombinant cPRL and cPRL-L via interaction with PRLR membrane-proximal ligand-binding domain, suggesting that like cPRL, cPRL-L is also a functional ligand of cPRLR. Collectively, characterization of cPRLR gene helps to elucidate the roles of PRLR and its ligands in birds and provides insights into the regulatory mechanisms of PRLR expression conserved in birds and mammals.

Regulation of Prolactin Receptor Gene Expression in the Rat Choroid Plexus via Transcriptional Activation of Multiple First Exons during Postnatal Development and Lactation

Prolactin (PRL) has numerous physiological functions that are mediated by its receptors in target cells. Expression of the rat PRL receptor (PRLR) gene is regulated in a tissue-specific manner via the transcriptional activation of five distinct first exons, i.e., E1(1), E1(2), E1(3), E1(4), and E1(5). In the present study, we investigated the expression profiles of these first exon variants of PRLR mRNA in the rat choroid plexus, which is considered to be a site of receptor-mediated PRL transport from the blood to cerebrospinal fluid. Real-time PCR analysis revealed that E1(3)-, E1(4)-, and E1(5)-PRLR mRNA expression levels increased in the choroid plexus in male and female rats during postnatal development, with markedly higher level of E1(4)-PRLR mRNA. In female rats, the E1(4)-PRLR mRNA expression levels increased markedly during lactation compared with the diestrus state, whereas there was no increase in the E1(3)- and E1(5)-PRLR mRNA levels. The E1(4)-PRLR mRNA expression pattern was similar to that of the total PRLR mRNA. The PRL plasma concentration generally correlated with the E1(4)-PRLR mRNA expression levels in both sexes. These findings suggest that PRLR gene expression in the choroid plexus is upregulated mainly via the transcriptional activation of the E1(4)-first exon.

Genetic effects of polymorphisms in the prolactin receptor gene on chicken reproductive traits

Prolactin receptor (PRLR) is a single transmembrane protein through which prolactin plays a wide variety of physiological roles in vertebrates. Markers of alleles for the PRLR gene were assessed for the association with six reproductive traits (bodyweight at first egg; egg weight at first egg; age at first egg; number of eggs at 300 days of age; bodyweight at 300 days of age; and egg weight at 300 days of age) in a single generation of the Erlang Mountain Chicken. Five single-nucleotide polymorphisms were detected in the PRLR gene by sequencing pooled DNA samples. Genotypes were identified using PCR-single strand conformational polymorphism and direct PCR-sequencing methods. The GLM procedure was used to estimate the association between genotypes and reproductive traits. The results showed that at the P1 locus, individuals with genotype TT had shorter age at first egg and greater number of eggs at 300 days of age than those with genotype CC (P &lt; 0.01). Our findings suggest that the single-nucleotide polymorphism g.-14A &gt; G at P1 locus could be a potential genetic marker for age at first egg and number of eggs at 300 days of age in the Erlang Mountain Chicken and haplotype ATGTT might be advantageous for reproductive traits.

Polymorphisms of LEP, LGB and PRLR in water buffalo

The polymorphisms of several genes including Leptin (LEP), beta-lactoglobulin (LGB) and Prolactin receptor (PRLR) have been shown to affect milk composition traits in dairy cattle. But, the effects of these polymorphisms on the milk traits of Philippine water buffalo are still unclear. In the Philippines, buffalo are the major milk producers most of which are the Philippine carabao (PC), the American Murrah Buffalo (AMB) and Bulgarian Murrah Buffalo (BMB). The LEP, LGB and PRLR genes are considered to be associated with milk production traits. The objective of the present study was to identify the single nucleotide polymorphisms (SNPs) in the LEP, LGB and PRLR genes of PC, AMB and BMB and to investigate the effect of the SNPs on milk production traits in these buffalo. Genetic polymorphisms were screened by DNA sequencing and 12 SNPs were detected in BMB; 5 SNPs were in LEP exon3 region (G14227A, G14343A, T14502C, C14526T, G14603A); 5 SNPs were in LGB exon 2 region (G1861C, A1900G, G1901T, T1948C, G1949A); 2 SNPs were in PRLR exon 6 (T59047C, T59109C). Also, 12 polymorphism sites between cattle and buffalo were identified. Our analysis of the association between SNPs and milk production traits should be useful in future studies of buffalo breeding to improve lactation performance.

Abstract A107: Variation in the prolactin and prolactin receptor genes and familial breast cancer

Abstract Background: Breast cancer aggregates within some families, accounting for about 25% of incident cases. Known genetic variants, such as BRCA1/BRCA2 mutations, account for less than 10% of these familial breast cancer cases, thus, research into additional risk or protective genetic factors for familial breast cancer may provide valuable information for risk stratification. Serum levels of prolactin have been associated with sporadic breast cancer risk in previous studies. We sought to test the hypothesis that variation in the genes coding for prolactin (PRL) and the prolactin receptor (PRLR) would be associated with increased or decreased risk of familial breast cancer. Methods: We designed a case-control study of probands recruited between 1998 and 2009 by the UCLA Family Cancer Registry; a population enriched with women having a strong family history of breast cancer and BRCA1/BRCA2 mutation carriers. Genotyping of tagSNPs in PRL (n=11) and PRLR (n=28) was performed in 351 unrelated women who developed breast cancer and 290 unaffected controls with similar family histories to the cases. Multivariate logistic regression models controlling for age, Ashkenazi Jewish heritage, education, and number of affected relatives were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between SNPs and familial breast cancer. Genotype specific ORs as well as per-allele (additive model) ORs were calculated. Results: Familial breast cancer risk was inversely associated with carriership of the minor alleles for three PRLR SNPs in the additive models, rs9292573 (OR=0.7, 95% CI=0.5-0.9), rs10805603 (OR=0.6, 95% CI=0.4-0.9), and rs1587607 (OR=0.7, 95% CI=0.5-1.0). PRLR SNP rs249522 was associated with increased risk of cancer in the additive model (OR=1.8, 95% CI =1.2-2.7). Minor allele carriers of the PRL SNP rs12210179, located in a putative transcription factor binding site, had a decreased risk of cancer in the additive model (OR=0.7, 95% CI=0.5-0.9). Conclusion: These data suggest that genetic variation in PRL and PRLR are associated with breast cancer in a population with a strong family history of breast cancer. Citation Format: Shehnaz K. Hussain, Mary Sehl, Daniel Conn, Janet S. Sinsheimer, Uma Dandekar, Jeanette Papp, Zuo-Feng Zhang, Patricia A. Ganz. Variation in the prolactin and prolactin receptor genes and familial breast cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A107.

Polymorphism of Prolactin Receptor Gene and its Association with Egg Production Traits in Erlang Mountainous Chicken

Polymorphism of Prolactin Receptor Gene and its Association with Egg Production Traits in Erlang Mountainous Chicken

Study of the association between alleles of the growth hormone receptor and prolactin receptor genes of bulls and the milk productivity of their daughters

A substitution of thyrosine for phenylalanine (F297Y) in the transmembrane domain of the growth hormone receptor (GHR) was tested for significance for breeding evaluation of bulls of the holstenized Black-and-White breed. The breeding value was estimated by the method of daughter yield deviation to contemporaries with modification. The frequency of genotype FF in the bulls examined was 0.37, lower than in Holstein bulls (0.67). The F297Y substitution exerted the greatest effect on the milk fat content (1.5 sigma) and milk yield (0.8 sigma) and a lower effect on the milk fat yield (0.6 sigma), milk protein yield (0.5 sigma), and milk protein content (0.6 sigma). The GHR4.2 single nucleotide substitution (SNP) in the promoter of the GHR gene did not affect the milk production traits. A substitution of asparagine for serine (S18N) in the transmembrane domain of the prolactin receptor (PRLR) was also examined, but it did not significantly affect the milk production parameters. The results are discussed in the context of the hypothesis that multiplicity of causal mutations of a particular gene is common and should be taken into account in the genetics of quantitative traits.

Physiological and hormonal aspects in female domestic pigeons (Columba livia) associated with breeding stage and experience

The present study examined the changes in serum biochemical values, hormone profiles and ovary prolactin receptor (PRLR) gene expression occurring in female domestic pigeons (Columba livia) under different breeding status and experience. The egg-laying pigeons had lower calcium, total protein, albumin, prolactin levels and higher oestrogen levels than those of incubating birds (p < 0.05). First-time breeders had higher (p < 0.05) progesterone levels and lower (p < 0.05) prolactin levels than that of experienced ones. The levels of oestrogen and follicle-stimulating hormone (FSH) increased with age (p < 0.05). The very old birds showed a pronounced increase (p < 0.05) in PRL, FSH and progesterone and a little decrease in oestrogen. Serum prolactin level was not correlated with the ovary PRLR mRNA expression pattern among all the pigeons. Results showed that serum physiological profile of female pigeons was correlated with breeding status, whereas reproductive hormone levels were correlated with advancing breeding experience. It was concluded that female pigeons had a good ability of recovering from nutrient loss after each breeding attempts, and the degradation of reproductive performance might be attributed to changes in the endocrine system.

Prolactin Receptor in Primary Hyperparathyroidism – Expression, Functionality and Clinical Correlations

BackgroundPrimary hyperparathyroidism (PHPT) is an endocrine disorder most commonly affecting women, suggesting a role for female hormones and/or their receptors in parathyroid adenomas. We here investigated the prolactin receptor (PRLr) which is associated with tumours of the breast and other organs.Methodology/Principal FindingsPRLr expression was investigated in a panel of 37 patients with sporadic parathyroid tumours and its functionality in cultured parathyroid tumour cells. In comparison with other tissues and breast cancer cells, high levels of prolactin receptor gene (PRLR) transcripts were demonstrated in parathyroid tissues. PRLr products of 60/70 kDa were highly expressed in all parathyroid tumours. In addition varying levels of the 80 kDa PRLr isoform, with known proliferative activity, were demonstrated. In parathyroid tumours, PRLr immunoreactivity was observed in the cytoplasm (in all cases, n = 36), cytoplasmic granulae (n = 16), the plasma membrane (n = 12) or enlarged lysosomes (n = 4). In normal parathyroid rim (n = 28), PRLr was uniformly expressed in the cytoplasm and granulae. In in vitro studies of short-term cultured human parathyroid tumour cells, prolactin stimulation was associated with significant transcriptional changes in JAK/STAT, RIG-I like receptor and type II interferon signalling pathways as documented by gene expression profiling. Moreover, PRLR gene expression in parathyroid tumours was inversely correlated with the patients’ plasma calcium levels.ConclusionsWe demonstrate that the prolactin receptor is highly abundant in human parathyroid tissues and that PRLr isoforms expression and PRLr subcellular localisation are altered in parathyroid tumours. Responsiveness of PRLr to physiological levels of prolactin was observed in the form of increased PTH secretion and altered gene transcription with significant increase of RIG-I like receptor, JAK-STAT and Type II interferon signalling pathways. These data suggest a role of the prolactin receptor in parathyroid adenomas.

Differences of Z chromosome and genomic expression between early- and late-feathering chickens

One duplicated segment on chicken Z chromosome is a causal mutation to the late-feathering phenotype. However, understanding biological process of the late-feathering formation is also of interest to chicken breeding and feather development theory. One hundred and thirty-seven valid single nucleotide polymorphisms (SNPs) from an SNP database were used to perform an association study of the Z chromosome in Xinghua chickens. Two SNPs, which were respectively on 9607480 bp and 10607757 bp, were significantly associated with feathering phenotypes. This result indicated the causal mutation of the late-feathering formation in Xinghua chickens was consistent with the previous report which showed the late-feathering locus ranged 9966364–10142688 bp on Z chromosome. Microarray expressions were implemented for six 1-day-old female Xinghua chicks. Compared to the early-feathering chicks, there were 249 and 83 upregulated and downregulated known genes in the late-feathering chicks. Forty-one genes were expressed in late-feathering chicks, but not in early-feathering ones. At least 14 significantly differentially expressed genes were directly related to keratin. In the region of the sex-linked feathering gene, only prolactin receptor (PRLR) gene was a significantly differentially expressed gene. Expression of PRLR in late-feathering chicks was 1.78-fold as that in early-feathering chicks. Late-feathering Wenchang chicks also had higher expression level of PRLR than early-feathering ones. This study suggested that increasing PRLR expression that resulted from the special variant on chicken Z chromosome caused the late-feathering phenotype.