Intracranial seeding of pituitary neuroendocrine tumor: a case report.

Background: Pituitary neuroendocrine tumors (PitNETs) are predominantly benign, though a minority may exhibit invasive tendencies. A diagnosis of metastatic PitNETs, in the absence of malignant histology, hinges on the identification of craniospinal and/or systemic metastases. Only a minority of PitNETs exhibit intracranial seeding. Notably, craniotomy for PitNETs excision is a prominent catalyst for iatrogenic seeding. Case Description: This article presented a compelling case that 15 years following craniotomy for the resection of a somatotroph PitNET, a lesion emerged at the left frontal base within the ethmoid sinus. Subsequent post-operative pathology unveiled a mature plurihormonal pituitary specific transcription factor 1 (PIT-1)-lineage PitNET. Growth hormone (GH) levels decreased significantly from 22.8 ng/mL pre-operation to 2 ng/mL post-operative, and concurrently, prolactin (PRL) levels decreased from 26.7 ng/mL pre-operation to 4.5 ng/mL post-operation. Furthermore, in the follow-up examination conducted 5 months after the operation, both GH and PRL levels were found to be within the normal range for the patient. This robustly suggested that the initial surgical procedure played a key role in the development of the lesion. Conclusions: This underscores the paramount significance of strictly adhering to the non-tumor removal during craniotomy for PitNETs excision. Regardless of apparent complete resection on imaging, it remains imperative to conduct routine follow-up evaluations, encompassing both imaging studies and hormone level assessments.

Plasma prolactin axis shift from placental to pituitary origin in late prepartum mice.

The placenta secretes a prolactin (PRL)-like hormone PRL3B1 (placental lactogen II), a luteotropic hormone essential for maintaining pregnancy until labor in mice. A report from 1984 examined the secretion pattern of PRL3B1 in prepartum mice. In the current study, we found contradictory findings in the secretion pattern that invalidate the previous report. By measuring maternal plasma PRL3B1 and PRL every 4 hrs from gestational day 17 (G17), we newly discovered that maternal plasma PRL3B1 levels decrease rapidly in prepartum C57BL/6 mice. Interestingly, the onset of this decline coincided with the PRL surge at G18, demonstrating a plasma prolactin axis shift from placental to pituitary origin. We also found that maternal plasma progesterone regression precedes the onset of the PRL shift. The level of Prl3b1 mRNA was determined by RT-qPCR in the placenta and remained stable until parturition, implying that PRL3B1 peptide production or secretion was suppressed. We hypothesized that production of the PRL family, the 25 paralogous PRL proteins exclusively expressed in mice placenta, would decrease alongside PRL3B1 during this period. To investigate this hypothesis and to seek proteomic changes, we performed a shotgun proteome analysis of the placental tissue using data-independent acquisition mass spectrometry (DIA-MS). Up to 5,891 proteins were identified, including 17 PRL family members. Relative quantitative analysis between embryonic day 17 (E17) and E18 placentas showed no significant difference in the expression of PRL3B1 and most PRL family members except PRL7C1. These results suggest that PRL3B1 secretion from the placenta is suppressed at G18 (E18).

Clinical Characteristics and Management of Cosecreting Thyroid Stimulating Hormone or Prolactin Pituitary Growth Hormone Adenomas: A Case-Control Study.

OBJECTIVE: Cosecreting thyroid stimulating hormone (TSH) or prolactin (PRL) in patients with pituitary growth hormone (GH) adenomas has been rarely reported. Our study aimed to elucidate their clinical characteristics. METHODS: We retrospectively collected data of 22 cases of cosecreting GH and TSH pituitary adenomas [(GH+TSH)oma] and 10 cases of cosecreting GH and PRL pituitary adenomas [(GH+PRL)oma] from Beijing Tiantan Hospital, Capital Medical University between January 2009 and January 2023. The clinical manifestation, preoperative hormone levels, imaging features, pathologic characteristics, and biochemical remission rates were compared among 335 patients with solo-secreting GH adenomas (GHoma) and 49 patients with solo-secreting TSH adenoma (TSHoma). Patients with (GH+TSH)oma and (GH+PRL)oma were grouped according to biochemical remission to explore the risk factors leading to biochemical nonremission. RESULTS: Cosecreting pituitary GH adenomas had various clinical manifestations and a larger tumor volume and were more likely to invade the cavernous sinus bilaterally and compress the optic chiasm. GH and TSH levels were lower in (GH+TSH)oma than in GHoma or TSHoma. Solo part remission was observed both in (GH+TSH)oma and (GH+PRL)oma. Cavernous sinus invasion was an independent risk factor for biochemical nonremission in patients with (GH+TSH)oma and (GH+PRL)oma. CONCLUSIONS: The clinical manifestation of (GH+TSH)oma and (GH+PRL)oma may be atypical. When screening for pituitary adenomas, a comprehensive evaluation of all pituitary target gland hormones is needed. Cosecreting pituitary GH adenomas are more aggressive and surgery is often unable to completely remove the tumor, requiring pharmacologic or radiological treatment if necessary. Clinicians should give high priority to biochemical remission, although solo part remission may occur.

Hyperprolactinaemia is common in Chinese premenopausal women with breast diseases.

Purpose: Hyperprolactinaemia has been proposed to play a role in breast lesions pathophysiology. Thus far, controversial results have been reported for the relationship between hyperprolactinaemia and breast lesions. Moreover, the prevalence of hyperprolactinaemia in a population with breast lesions is scarcely reported. We aimed to investigate the prevalence of hyperprolactinaemia in Chinese premenopausal women with breast diseases, and explore the associations between hyperprolactinaemia with different clinical characteristics. Methods: This was a retrospective cross-sectional study performed in the department of breast surgery of Qilu hospital of Shandong University. Overall, 1,461 female patients who underwent the serum prolactin (PRL) level assay before breast surgery from January 2019 to December 2020 were included. Patients were divided into two groups: before and after menopause. Data were analyzed using SPSS 18.0 software. Results: The results showed an elevated PRL level in 376 of the 1,461 female patients with breast lesions (25.74%). Furthermore, the proportion of hyperprolactinemia among premenopausal patients with breast disease (35.75%, 340/951) was significantly higher than among postmenopausal patients with breast disease (7.06%, 36/510). In premenopausal patients, the proportion of patients with hyperprolactinaemia and the mean serum PRL level were significantly higher in those diagnosed with fibroepithelial tumours (FETs) and in younger patients (aged < 35 years) than in those with non-neoplastic lesions and in those aged ≥ 35 years (both p < 0.05). Especially, the prolactin level exhibited steady ascending tendency for positive correlation with FET. Conclusion: Hyperprolactinaemia is prevalent in Chinese premenopausal patients with breast diseases, especially in those with FETs, which implies a potential association, to some extent, between the PRL levels in various breast diseases.

Relation between vitamin D and adolescents' serum prolactin.

Introduction: To detect whether there is a relation between vitamin D (Vit. D) and adolescents' serum prolactin (PRL) or not. Material and methods: Hundred and seventy-six adolescent girls were recruited for the current study, which was conducted in West Kazakhstan (Aktobe) over two years. After thorough evaluation, blood samples were taken from adolescents to measure thyroid stimulating hormone (TSH), free thyroxine (T4), PRL, glycosylated hemoglobin and 25(OH)D. The studied adolescents were classified into study group [25(OH)D deficient] and controls [normal 25(OH)D]. The acquired adolescents' variables were analyzed using the Student t-test and Pearson's correlation. Results: The serum TSH and PRL were statistically higher in the study group than normal controls (3.73 ±1.45 mIU/ml and 47.5 ±7.6 ng/ml vs. 2.67 ±1.0 and 10.8 ±5.1, respectively), (p = 0.0003 and p = 0.0001, respectively). The free T4 was statistically lower in the study group than normal controls (1.4 ±0.6 ng/ml vs. 1.5 ±0.4), (p = 0.0001). Strong negative associations between the serum PRL and 25(OH)D [r = -0.803 (p < 0.00001)], and between the serum PRL and free T4 [r = -0.6959 (p < 0.00001)] were detected in this study. Additionally, there was a strong positive association between the serum PRL and TSH [r = 0.8137 (p < 0.00001)]. Conclusions: A strong negative association between the serum PRL and 25(OH)D and a strong positive association between the serum PRL and TSH were detected in this study. This study recommends further studies to confirm the relation between Vit. D and PRL and screening Vit. D deficient adolescents for PRL and thyroid disorders.

Prolactin receptor gene transcriptional control, regulatory modalities relevant to breast cancer resistance and invasiveness.

The prolactin receptor (PRLR) is a member of the lactogen/cytokine receptor family, which mediates multiple actions of prolactin (PRL). PRL is a major hormone in the proliferation/differentiation of breast epithelium that is essential for lactation. It is also involved in breast cancer development, tumor growth and chemoresistance. Human PRLR expression is controlled at the transcriptional level by multiple promoters. Each promoter directs transcription/expression of a specific non-coding exon 1, a common non-coding exon 2 and coding exons E3-11. The identification of exon 11 of PRLR led to finding of alternative spliced products and two novel short forms (SF) that can inhibit the long form (LF) of PRLR activity with relevance in physiological regulation and breast cancer. Homo and heterodimers of LF and SF are formed in the absence of PRL that acts as a conformational modifier. Heterodimerization of SF with LF is a major mechanism through which SF inhibits some signaling pathways originating at the LF. Biochemical/molecular modeling approaches demonstrated that the human PRLR conformation stabilized by extracellular intramolecular S-S bonds and several amino acids in the extracellular D1 domain of PRLR SF are required for its inhibitory actions on PRLR LF-mediated functions. Studies in breast cancer cells demonstrated that the transcription of PRLR was directed by the preferentially utilized PIII promoter, which lacks an estrogen responsive element. Complex formation of non-DNA bound ERα dimer with Sp1 and C/EBPß dimers bound to their sites at the PRLR promoter is required for basal activity. Estradiol induces transcriptional activation/expression of the PRLR gene, and subsequent studies revealed the essential role of autocrine PRL released by breast cancer cells and CDK7 in estradiol-induced PRLR promoter activation and upregulation. Other studies revealed stimulation of the PRLR promoter activity and PRLR LF protein by PRL in the absence of estrogen via the STAT5/phospho-ERα activation loop. Additionally, EGF/ERBB1 can induce the transcription of PRLR independent of estrogen and prolactin. The various regulatory modalities contributing to the upregulation of PRLR provide options for the development of therapeutic approaches to mitigate its participation in breast cancer progression and resistance.

Prolactin Expression in the Baboon (Papio hamadryas) Eye.

Prolactin (PRL) is a hormone expressed in lactotrophs cells of the pituitary gland in primates. Extra pituitary expression of PRL has been reported, including the eye; however, expression in the developing eye of primates is limited. The aim of the study was determining the expression of PRL and PRL receptor (PRLR) (mRNAs and proteins) in adult and fetal baboon (Papio hamadryas) ocular tissues. METHODS: We analyzed PRL and PRLR in baboon eyes tissues by immunofluorescence. The mRNAs of PRL and PRLR were detected by RT-PCR, cDNA was cloned, and sequenced. Furthermore, we performed a phylogenetic analysis to identify the evolutionary forces that underlie the divergence of PRL and PRLR primate genes. RESULTS: We observed the expression of PRL and PRLR (mRNAs and proteins) in all retinal cell lineages of fetal and adult baboon. PRL and PRLR fit the hypothesis of evolutionary purifying gene selection. CONCLUSIONS: mRNA and protein of PRL and PRLR are expressed in fetal and adult baboon retinal tissue. PRL may trigger autocrine and paracrine-specific actions in retinal cell lines.

Prolactin: The Third Hormone in Breast Cancer.

Prolactin coordinates with the ovarian steroids to orchestrate mammary development and lactation, culminating in nourishment and an increasingly appreciated array of other benefits for neonates. Its central activities in mammary epithelial growth and differentiation suggest that it plays a role(s) in breast cancer, but it has been challenging to identify its contributions, essential for incorporation into prevention and treatment approaches. Large prospective epidemiologic studies have linked higher prolactin exposure to increased risk, particularly for ER+ breast cancer in postmenopausal women. However, it has been more difficult to determine its actions and clinical consequences in established tumors. Here we review experimental data implicating multiple mechanisms by which prolactin may increase the risk of breast cancer. We then consider the evidence for role(s) of prolactin and its downstream signaling cascades in disease progression and treatment responses, and discuss how new approaches are beginning to illuminate the biology behind the seemingly conflicting epidemiologic and experimental studies of prolactin actions across diverse breast cancers.

Prolactin Inducible Protein, but Not Prolactin, Is Present in Human Tears, Is Involved in Tear Film Quality, and Influences Evaporative Dry Eye Disease.

Purpose: Decreased production of the aqueous component of the tear film is an important cause of the development of dry eye disease (DED). Tear production is influenced by hormones and hormone-like factors. Prolactin (PLR), a multifunctional pituitary gland hormone, is regularly present in the lacrimal gland of rats and rabbits. In humans, serum PLR concentration correlates with tear quality. To gain deeper insights of possible effects of PRL, prolactin receptor (PRLR) and prolactin inducible protein (PIP), we analyzed the three proteins in the human lacrimal apparatus and in reflex tears of healthy volunteers as well as patients suffering from DED. Methods: Gene expression of PRLR and PIP was analyzed by RT-PCR in cadaveric human lacrimal gland and ocular surface tissues, immortalized human corneal epithelial cells (HCE and hTEPI) and human Meibomian gland epithelial cells (HMGECs). At the protein level, the expression and localization of PRL, PRLR and PIP in formalin-fixed paraffin sections of the lacrimal apparatus were studied by immunohistochemistry. In addition, tear fluid from DED patients and healthy volunteers was analyzed by ELISA to determine the concentration of PRL and PIP. Results: RT-PCR analyses revealed gene expression of PRLR and PIP in human tissue samples of cornea, lacrimal glands, and eyelids, whereas only PIP, but not PRLR, was detectable in immortalized corneal epithelial cells. Immunohistochemistry revealed for the first time the expression and localization of PRL, PRLR, and PIP in human tissues of the lacrimal apparatus and at the ocular surface. PRL and PRLR were detectable in corneal epithelium, lacrimal glands, and Meibomian glands. Reflex tears from DED patients revealed significantly increased PIP concentrations, whereas PRL was undetectable in tears of DED patients and healthy volunteers. Conclusion: PRL, PRLR, and PIP are found in the lacrimal apparatus and on the ocular surface. PIP, but not PRL, is present in human tears and appears to be involved in the physiology of tear film quality. Our clinical data revealed that PIP may affect tear quality, but further functional analyses are needed to fully elucidate the effects of PRL and PIP-associated factors in tear secretion as well as in the connection of DED.

Development of Vasoinhibin-Specific Monoclonal Antibodies.

Vasoinhibin is a protein hormone with antiangiogenic, antivasodilatatory, and antivasopermeability effects generated by the proteolytic cleavage of prolactin. The discovery of its role in diabetic retinopathy and peripartum cardiomyopathy led to the evaluation of new pharmacological treatments in clinical interventional trials. However, the quantitative evaluation of vasoinhibin in biological samples from patients has not been possible due to the lack of vasoinhibin-specific antibodies. Recently, loop 1 of vasoinhibin was identified to have a different three-dimensional structure compared to PRL, and thus to contain vasoinhibin-specific epitopes. Here, we report the development of two sets of vasoinhibin-specific monoclonal antibodies against two neighboring regions of the vasoinhibin loop 1. An experimental sandwich ELISA with two monoclonal anti-vasoinhibin antibodies was developed, which had no cross-reactivity to recombinant human full-length prolactin. The ELISA had a quantitation limit of 100 ng/ml, and intra-assay- and inter-assay coefficients of variation of 12.5% and 14%, respectively. The evaluation of 15 human serum samples demonstrated concentrations of below limit of detection (n=3), below limit of quantitation (n=1) and between 0.23 µg/ml (230 ng/ml) to 605 µg/ml (n=12) in the quantifiable range. Despite the high specificity of the monoclonal-monoclonal antibody sandwiches which discriminate vasoinhibin from PRL, there might be cross-reactivities by serum proteins other than vasoinhibin. A fully established vasoinhibin ELISA may support diagnostic and therapeutic measures in vascular diseases.

A retrospective analysis of recurrence risk factors for granulomatous lobular mastitis in 130 patients: more attention should be paied to prolactin level.

BACKGROUND: Granulomatous lobular mastitis (GLM) is a benign chronic inflammatory breast disease with indecisive etiology and easy recurrence, and seriously affects physical and mental health of women. This study aims to discover the factors associated with the recurrence of GLM and provide some new thoughts for the treatment. METHODS: We retrospectively collected clinical data of GLM patients from January 2010 to June 2019. Patients were divided into no recurrence group (group A) and recurrence group (group B). Demographic data and clinical features were compared in two groups. RESULTS: There were 103 (79.23%) patients in group A and 27 (20.77%) in group B. In univariate analysis, body mass index (BMI), the difference of prolactin (PRL) level before and after treatment and follicle-stimulating hormone (FSH)/luteinizing hormone (LH) were associated with the recurrence of GLM. Moreover, the difference of PRL level before and after treatment was the independent risk factor of recurrence and patients presenting with higher PRL after treatment than before treatment had a higher risk of recurrence [odds ratio (OR) 21.405, 95% confidence interval (CI): 1.702-269.233, P=0.018]. CONCLUSIONS: Obesity or overweight and FSH/LH had association with GLM recurrence, and the difference of PRL level before and after treatment is the independent risk factor of recurrence. Clinical examination of hormone levels especially the PRL level should not be ignored during and even after the treatment of GLM.

A novel 23 bp indel mutation in PRL gene is associated with growth traits in Luxi Blackhead sheep.

Prolactin is a highly versatile pituitary hormone with multiple biological functions. PRL expression is regulated by POU1F1 and the prophet of POU1F1 (PROP1). The aim of this study was to investigate the indel variations in ovine PRL and the directly related (PROP1 and POU1F1) genes, and their associations with growth traits in Luxi Blackhead (LXBH) sheep. A monomorphism in PROP1 and POU1F1 genes, and one novel 23-bp insertion mutation in the PRL gene, were identified in LXBH sheep. The 23 bp insertion mutation within PRL gene was significantly associated with several body measurements (e.g., body weight, body height) in sheep of different ages (p < 0.05). Ram lambs (p = 0.036) of genotype insertion/insertion (II) had significantly higher body weights. Weaners (p = 0.018) of genotypes insertion/insertion (II) and insertion/deletion (ID) also had significantly higher body weights compared with male sheep of deletion/deletion (DD) genotype. Moreover, among ewe lambs, individuals of genotype insertion/insertion (II) had a higher paunch girth compared to those with other genotypes (p = 0.044). These findings indicate that a 23 bp indel variant of the ovine PRL gene is correlated with body measurements in LXBH sheep. The findings have potential utility for sheep breeding programs based on marker-assisted selection.

Indel variants within the PRL and GHR genes associated with sheep litter size.

Growth hormone and prolactin belong to the class of peptide hormones that have a wide range of regulatory functions. In this study, polymorphisms of growth hormone receptor (GHR) and prolactin (PRL) genes were analysed as candidate genes, which are responsible for the litter size in Australian White (AUW) sheep. According to the statistical analyses results, the polymorphism information content (PIC) values of the PRL-P1-ins-23 bp, GHR-P2-del-23 bp and GHR-P8-del-23 bp were 0.371, 0.366 and 0.375, respectively, which indicates the high genetic polymorphism in AUW sheep. Moreover, all indel loci are not conformed to the HWE (p < .05). Further, our findings revealed that the PRL-P1-ins-23 bp polymorphism in the ovine PRL gene was significantly related to the first parity litter size (p = .001) and the DD genotype displaying the highest genotypic mean. Meanwhile, the GHR-P2-del-23 bp and GHR-P8-23 bp indels in the ovine GHR gene were significantly correlated with first parity litter size (p < .05), and the individuals with the genotype II showed significantly higher litter size than others. Collectively, these results demonstrated that our findings could be useful for future sheep breeding strategies based on the molecular-assisted selection (MAS).

Serum prolactin levels across pregnancy and the establishment of reference intervals.

BACKGROUND: Reference intervals (RIs) play key roles in clinical diagnosis, treatment and prognosis. However, RIs for clinical testing tend to be confined to the general population, and RIs for pregnant women are not very comprehensive. In this study, we establish RIs for prolactin (PRL) in healthy pregnant and postpartum women in the Chinese population. METHODS: Healthy pregnant women (n=378) were divided into groups according to whether they were in the first, second or third trimester of pregnancy. Healthy postpartum women (n=493) were separated into four groups according to mode of delivery as follows: postvaginal (24 and 48 h) or postcesarean (24 and 48 h). Healthy, non-pregnant women (n=123) were enrolled as a control group. Serum PRL levels were measured by electrochemiluminescence immunoassay, and RIs were established for each group. RESULTS: The RIs for PRL were as follows: healthy non-pregnant women, 178.89-757.52 µIU/mL; first trimester, 621.20-3584.00 µIU/mL; second trimester, 1432.00-5349.68 µIU/mL; third trimester, 4087.33-9733.65 µIU/mL; 24 and 48 h postvaginal delivery (combined), 7865.36-10998.86 µIU/mL; and 24 and 48 h postcesarean delivery, 4556.41-7675.99 and 6578.45-9980.45 µIU/mL, respectively. CONCLUSIONS: PRL RIs for pregnant women were established according to trimester, days postpartum and mode of delivery, thus providing a clinical reference for medical staff.

Neuroendocrine Control of Broodiness.

In the majority of vertebrates, survival of offspring to sexual maturation is important for increasing population size, and parental investment in the young is important for reproductive success. Consequently, parental care is critical for the survival of offspring in many species, and many vertebrates have adapted this behavior to their social and ecological environments. Parental care is defined as any behavior that is performed in association with one's offspring (Rosenblatt, Mayer, Siegel. Maternal behavior among nonprimate mammals. In: Adler, Pfaff, Goy, editors. Handbook of behavioral neurobiology. New York: Plenum; 1985. p. 229-98) and is well characterized in mammals and birds. In birds (class Aves), this is due to the high level of diversity across species. Parental behavior in birds protects the young from intruders, and generally involves nest building, incubation, and broody behavior which protect their young from an intruder, and the offspring are reared to independence. Broodiness is complexly regulated by the central nervous system and is associated with multiple hormones and neurotransmitters produced by the hypothalamus and pituitary gland. The mechanism of this behavior has been extensively characterized in domestic chicken (Gallus domesticus), turkey (Meleagris gallopavo), and pigeons and doves (family Columbidae). This chapter summarizes broodiness in birds from a physiology, genetics, and molecular biology perspective.

[Effects of acupuncture combined with Rule granule on breast tissue, prolactin and receptor expression in rats with mammary gland hyperplasia].

OBJECTIVE: To observe the effects of acupuncture combined with Rule granule on breast tissue, prolactin(PRL) and prolactin receptor (PRLR) expression in rats with mammary gland hyperplasia (MGH), and to explore its action mechanism to provide reference for clinical treatment of MGH. METHODS: Fifty-five female SD rats were randomly divided into a blank group, a model group, an acupuncture group, a Rule granule group and a combination group. Except the blank group, the rats in the remaining groups were treated with combined stimulation of estrogenic and progestational hormone to establish MGH model. After model establishment, the rats in the acupuncture group were treated with acupuncture at Plan A of "Tianzong" (SI 11), "Ganshu" (BL 18), "Zusanli" (ST 36) and Plan B of "Wuyi" (ST 15), "Hegu" (LI 4), "Danzhong" (CV 17). Each plan was selected for one acupuncture treatment, and two plans were used alternately. The rats in the Rule granule group were treated with oral administration of granule, 3 mL per times. The rats in the combination group were treated with the same Rule granule, followed by acupuncture, once a day. After consecutive 30-day treatment, blood sample was collected from abdominal aorta; ELISA method was applied to measure the contents of PRL; the HE slice of mammary gland was observed under light microscope; the SABC immunohistochemical method was applied to measure the positive expression of PRLR. RESULTS: The morphology of breast tissue in the model group was consistent with MGH. Compared with the blank group, the serum PRL and the expression of PRLR were increased significantly in the model group (both P<0.01). Compared with the model group, the hyperplasia of mammary gland in each treatment group was improved, and serum PRL and expression of PRLR were significantly reduced (P<0.05, P<0.01), which were more significant in the combination group (both P<0.05). CONCLUSION: Acupuncture, Rule granule and its combination could effectively treat MGH, which is likely to reduce the level of serum PRL and inhibit the binding of PRL to PRLR, as a result, the level of E2 is indirectly inhibited, and the hyperplastic mammary gland is recovered. Compared with acupuncture or Rule granule, the combination of both has better overall efficacy.

Effects of acupuncture combined withgranule on breast tissue, prolactin and receptor expression in rats with mammary gland hyperplasia / 中国针灸

<p><b>OBJECTIVE</b>To observe the effects of acupuncture combined withgranule on breast tissue, prolactin(PRL) and prolactin receptor (PRLR) expression in rats with mammary gland hyperplasia (MGH), and to explore its action mechanism to provide reference for clinical treatment of MGH.</p><p><b>METHODS</b>Fifty-five female SD rats were randomly divided into a blank group, a model group, an acupuncture group, a Rule granule group and a combination group. Except the blank group, the rats in the remaining groups were treated with combined stimulation of estrogenic and progestational hormone to establish MGH model. After model establishment, the rats in the acupuncture group were treated with acupuncture at Plan A of "Tianzong" (SI 11), "Ganshu" (BL 18), "Zusanli" (ST 36) and Plan B of "Wuyi" (ST 15), "Hegu" (LI 4), "Danzhong" (CV 17). Each plan was selected for one acupuncture treatment, and two plans were used alternately. The rats in the Rule granule group were treated with oral administration of granule, 3 mL per times. The rats in the combination group were treated with the samegranule, followed by acupuncture, once a day. After consecutive 30-day treatment, blood sample was collected from abdominal aorta; ELISA method was applied to measure the contents of PRL; the HE slice of mammary gland was observed under light microscope; the SABC immunohistochemical method was applied to measure the positive expression of PRLR.</p><p><b>RESULTS</b>The morphology of breast tissue in the model group was consistent with MGH. Compared with the blank group, the serum PRL and the expression of PRLR were increased significantly in the model group (both<0.01). Compared with the model group, the hyperplasia of mammary gland in each treatment group was improved, and serum PRL and expression of PRLR were significantly reduced (<0.05,<0.01), which were more significant in the combination group (both<0.05).</p><p><b>CONCLUSION</b>Acupuncture,granule and its combination could effectively treat MGH, which is likely to reduce the level of serum PRL and inhibit the binding of PRL to PRLR, as a result, the level of Eis indirectly inhibited, and the hyperplastic mammary gland is recovered. Compared with acupuncture orgranule, the combination of both has better overall efficacy.</p>

Interaction of pituitary hormones and expression of clock genes modulated by bone morphogenetic protein-4 and melatonin.

Functional interaction of clock genes and pituitary hormones was investigated by focusing on bone morphogenetic protein (BMP)-4 and melatonin actions in anterior pituitary cells. A significant correlation between the mRNA expression of proopiomelanocortin (POMC) and Per2 was revealed in serial cultures of corticotrope AtT20 cells. Knockdown of Per2 expression by siRNA in AtT20 cells resulted in a significant reduction of POMC mRNA level with or without corticotropin-releasing hormone (CRH) stimulation. Treatments with BMP-4 and melatonin, both of which suppress POMC expression, reduced Per2 mRNA as well as protein levels in AtT20 cells. On the other hand, in lactosomatotrope GH3 cells, an expressional correlation was found between prolactin (PRL) and Clock mRNA levels, which was attenuated in the presence of forskolin treatment. The siRNA-mediated knockdown of Clock expression, but not that of Bmal1, significantly reduced PRL mRNA levels in GH3 cells. Interestingly, Clock mRNA and protein levels did not fluctuate with melatonin, BMP-4 or forskolin treatment, although Bmal1 expression was significantly increased by forskolin treatment. Collectively, a significant correlation between the expression of POMC and Per2 and that between PRL and Clock were uncovered in corticotrope and lactosomatotrope cells, respectively. Per2 expression was inhibited by POMC modulators including melatonin and BMP-4, while Clock expression was steadily maintained. Thus, the effects of melatonin and BMP-4 on clock gene expression may imply differential stability of circadian rhythms of adrenocorticotropin (ACTH) and PRL secreted from the anterior pituitary.