OBJECTIVE: To explore the mechanism of acupuncture on improving ovarian hypofunction in aged rats from two perspectives: the overall regulation of the hypothalamic-pituitary-ovarian (HPO) axis and the local ovarian follicle stimulating hormone (FSH)/cyclic adenosine monophosphate (cAMP) signaling pathway. METHODS: Six 3-month-old female SPF-grade Sprague-Dawley (SD) rats were selected as the blank group. Another twelve 9-month-old female SD rats were randomly divided into a model group and an acupuncture group, with six rats in each. The acupuncture group received acupuncture at "Baihui" (GV20), "Guanyuan" (CV4), and bilateral "Ciliao" (BL32) for 20 min per session, once every other day, for a total of 10 sessions. Vaginal smear tests were performed daily to observe the estrous cycle of the rats. Ovarian morphology was observed using HE staining, and follicles at various stages were counted. ELISA was used to detect levels of serum FSH, luteinizing hormone (LH), estradiol (E₂), anti-müllerian hormone (AMH), hypothalamic gonadotropin-releasing hormone (GnRH), pituitary FSH and LH, and ovarian cAMP. Immunohistochemistry and Western blot were used to detect the protein expression of ovarian cAMP protein kinase catalytic subunit, FSH receptor (FSHR), and P450. Real-time quantitative PCR was used to measure mRNA expression levels of FSHR and P450 in ovarian tissue. RESULTS: Compared with the blank group, the model group showed an increased rate of estrous cycle disorder (P<0.01), reduced granulosa cell layers with blurred boundaries and disordered arrangement, decreased numbers of developing follicles at all stages, and increased numbers of atretic follicles (P<0.01); the serum levels of FSH and LH were increased (P<0.01), while E₂ and AMH levels were decreased (P<0.01); the hypothalamic GnRH and pituitary FSH and LH levels were elevated (P<0.01), and ovarian cAMP level was decreased (P<0.01); the positive expression and protein expression of ovarian P450, cAMP protein kinase catalytic subunit, and FSHR were reduced (P<0.01), and ovarian FSHR and P450 mRNA expression was decreased (P<0.01). Compared with the model group, the acupuncture group showed a reduced rate of estrous cycle disorder (P<0.01), clear granulosa cell margins, increased numbers of primordial and secondary follicles, and decreased numbers of atretic follicles (P<0.01); the serum FSH and LH levels were decreased (P<0.01, P<0.05), while E₂ and AMH levels were increased (P<0.05, P<0.01); the hypothalamic GnRH and pituitary FSH and LH levels were decreased (P<0.01, P<0.05), and ovarian cAMP level was increased (P<0.01); the positive expression and protein expression of ovarian P450, cAMP protein kinase catalytic subunit, and FSHR were elevated (P<0.01), and ovarian FSHR and P450 mRNA expression was increased (P<0.01). CONCLUSION Acupuncture could delay ovarian hypofunction in aged rats, possibly through regulating the HPO axis and the FSH/cAMP signaling pathway.
Animals ; Female ; Rats ; Rats, Sprague-Dawley ; Follicle Stimulating Hormone/genetics* ; Acupuncture Therapy ; Ovary/metabolism* ; Signal Transduction ; Humans ; Cyclic AMP/metabolism* ; Hypothalamo-Hypophyseal System/metabolism* ; Aging/metabolism* ; Hypothalamus/metabolism* ; Pituitary Gland/metabolism* ; Gonadotropin-Releasing Hormone/metabolism*

A long-held belief is that pituitary hormones bind to their cognate receptors in classical target glands to actuate their manifold functions. However, a number of studies have shown that multiple types of pituitary hormone receptors are widely expressed in non-classical target organs. Each pituitary gland-derived hormone exhibits a wide range of nonconventional biological effects in these non-classical target organs. Herein, the extra biological functions of pituitary hormones, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotrophic hormone, and prolactin when they act on non-classical organs were summarized, defined by the novel concept of an "atypical pituitary hormone-target tissue axis." This novel proposal explains the pathomechanisms of abnormal glucose and lipid metabolism, obesity, hypertension, fatty liver, and atherosclerosis while offering a more comprehensive and systematic insights into the coordinated regulation of environmental factors, genetic factors, and neuroendocrine hormones on human biological functions. The continued exploration of the physiology of the "atypical pituitary hormone-target tissue axis" could enable the identification of novel therapeutic targets for metabolic diseases.
Humans ; Pituitary Hormones/metabolism* ; Luteinizing Hormone ; Follicle Stimulating Hormone ; Prolactin ; Pituitary Gland/metabolism*

Sleep deprivation (SD) has many deleterious health effects and occurs in more than 70% of pregnant women. However, the changes in sex hormones and relevant mechanisms after SD have not been well clarified. The aim of the present study was to explore the effects of SD on the secretion of sex hormones and the underlying mechanisms. Twelve pregnant Wistar rats were divided into control (CON, n = 6) and SD (n = 6) groups. Pregnant rats in the SD group were deprived of sleep for 18 h, and allowed free rest for 6 h, and then the above procedures were repeated until delivery. The CON group lived in a 12 h light/dark light cycle environment. Estradiol (E2) and progesterone (P4) levels were detected by enzyme-linked immunosorbent assay (ELISA), and the expression of circadian clock genes, Bmal1, Clock and Per2, in hypothalamus and pituitary gland tissues were evaluated by immunohistochemistry (IHC) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The PI3K and Akt phosphorylation levels in the hypothalamic and pituitary tissues were determined by Western blot. The results showed that, compared with the CON group, the SD group exhibited significantly reduced serum E2 and P4 levels, down-regulated Bmal1, Clock and Per2 expression, as well as decreased phosphorylation levels of PI3K and Akt. But there was no significant difference of the total PI3K and Akt protein expression levels between the two groups. These results suggest that SD might affect the expression of the circadian clock genes in the hypothalamus and pituitary via PI3K/Akt pathway, and subsequently regulate the secretion of sex hormones in the pregnant rats, which hints the important roles of SD-induced changes of serum sex hormone levels in the pregnant rats.
ARNTL Transcription Factors/metabolism* ; Animals ; Circadian Clocks/physiology* ; Circadian Rhythm/genetics* ; Female ; Gene Expression Regulation/genetics* ; Gonadal Steroid Hormones/metabolism* ; Hypothalamus/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Pituitary Gland/metabolism* ; Pregnancy ; Progesterone ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats ; Rats, Wistar ; Signal Transduction ; Sleep Deprivation/metabolism*

OBJECTIVE: To investigate the mechanism by which doublecortin promotes the recovery of cytoskeleton in arginine vasopressin (AVP) neurons in rats with electrical lesions of the pituitary stalk (PEL). METHODS: Thirty-two SD rats were randomized into PEL group with electrical lesions of the pituitary stalk through the floor of the skull base (=25) and sham operation group (=7), and the daily water consumption (DWC), daily urine volume (DUV) and urine specific gravity (USG) of the rats were recorded. Four rats on day 1 and 7 rats on each of days 3, 7 and 14 after PEL as well as the sham-operated rats were sacrificed for detection of the expressions of β-Tubulin (Tuj1), doublecortin and caspase- 3 in the AVP neurons of the supraoptic nucleus using immunofluorescence assay and Western blotting. RESULTS: After PEL, the rats exhibited a typical triphasic pattern of diabetes insipidus, with the postoperative days 1-2 as the phase one, days 3-5 as the phase two, and days 6-14 as the phase three. Immunofluorescent results indicated the repair of the AVP neurons evidenced by significantly increased doublecortin expressions in the AVP neurons following PEL; similarly, the expression of Tuj1 also increased progressively after PEL, reaching the peak level on day 7 after PEL. The apoptotic rates of the AVP neurons exhibited a reverse pattern of variation, peaking on postoperative day 3 followed by progressive reduction till day 14. Western blotting showed that the expressions of c-Jun and p-c-Jun were up-regulated significantly on day 3 ( < 0.05) and 7 ( < 0.01) after PEL, while an upregulated p-JNK expression was detected only on day 3 ( < 0.05), as was consistent with the time-courses of neuronal recovery and apoptosis after PEL. CONCLUSIONS JNK/c-Jun pathway is activated after PEL to induce apoptosis of AVP neurons in the acute phase and to promote the repair of neuronal cytoskeleton by up-regulation of doublecortin and Tuj1 expressions.
Animals ; Apoptosis ; Arginine Vasopressin ; pharmacology ; Cytoskeleton ; metabolism ; MAP Kinase Signaling System ; Neurons ; cytology ; Pituitary Gland ; cytology ; injuries ; Proto-Oncogene Proteins c-jun ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Regeneration ; Tubulin ; metabolism

BACKGROUNDImmunoglobulin G4-related disease (IgG4-RD) is a newly recognized systemic disease that can involve multiple organs and various clinical phenotypes. The purpose of this study was to analyze different types of organ involvement in IgG4-RD patients in China.

METHODSWe conducted a prospective cohort study on IgG4-RD patients to analyze the clinical manifestations and rare features of IgG4-RD. Patients were grouped into different types according to organ involvement regarding organ number and organ site. The constituent ratio in different types was also analyzed.

RESULTSA total of 200 IgG4-RD patients, with a male:female ratio of 2.08:1, were grouped into different types. Cases having involvement of two or three organs were the most common whereas the fewest number of patients had multi-organ (≥4) involvement. Serum IgG4 and IgE levels, IgG4/IgG ratio, and percentage of eosinophils increased as the number of involved organs increased. In addition, constituent ratio analysis revealed that patients with salivary gland/lacrimal gland swelling, who also constituted the largest number of IgG4-RD patients, had higher serum IgG4 concentrations and IgG4/IgG values, had higher percentage of Eos, and were more likely to have had a history of allergies relative to patients with internal organ involvement.

CONCLUSIONSThe characteristic feature of IgG4-RD is multiple organ involvement with various clinical manifestations and different types. Although serum IgG4 levels increased with the number of involved organs, serum IgG4 levels were higher for those patients with salivary gland/lacrimal gland swelling compared with those with internal organ involvement. Thus, valuable clues to the differential diagnosis of IgG4-RD could be obtained by examining the clinical patterns of organ involvement.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Autoimmune Diseases ; complications ; pathology ; Eosinophils ; metabolism ; Female ; Humans ; Immunoglobulin E ; blood ; Immunoglobulin G ; blood ; Kidney ; pathology ; Lacrimal Apparatus ; pathology ; Lung ; pathology ; Male ; Middle Aged ; Pituitary Gland ; pathology ; Prospective Studies ; Prostate ; pathology ; Salivary Glands ; pathology ; Thyroid Gland ; pathology ; Uterus ; pathology ; Young Adult

Bone is a dynamic tissue undergoing life-long remodeling, a process of bone resorption by osteoclast and bone formation by osteoblast, regulated by diverse hormones including estrogen. Recently, several pituitary hormones have been identified as a modulator of this process. Here, we reviewed the role of thyroid stimulating hormone signaling per se in bone metabolism.
Bone Remodeling ; Bone Resorption ; Estrogens ; Metabolism* ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Pituitary Hormones ; Thyroid Gland* ; Thyrotropin*

Bone is a dynamic tissue undergoing life-long remodeling, a process of bone resorption by osteoclast and bone formation by osteoblast, regulated by diverse hormones including estrogen. Recently, several pituitary hormones have been identified as a modulator of this process. Here, we reviewed the role of thyroid stimulating hormone signaling per se in bone metabolism.
Bone Remodeling ; Bone Resorption ; Estrogens ; Metabolism* ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Pituitary Hormones ; Thyroid Gland* ; Thyrotropin*

OBJECTIVETo investigate the expression and significance of CD151 in pituitary adenomas.

METHODSThirty-six pituitary adenomas were collected immediately after surgery together with five normal pituitary tissue. Real time-PCR, Western blot and immunohistochemistry analysis were performed to detect the expression of CD151 mRNA and protein in thirty-six pituitary adenomases and five normal pituitary tissues.

RESULTSThe expression of CD151 in all pituitary adenomases was observed to be significantly higher than that in normal pituitary tissues by Western blot, real time PCR, and immunohistochemistry analysis (P < 0.01). The expression levels of protein and mRNA in invasive pituitary adenomas were much higher than those in non-invasive pituitary adenomas (P < 0.01).

CONCLUSIONThe results suggested that the expression of CD151 was closely correlated with malignant degree of pituitary adenomas, which indicated the expression of CD151 was intimately correlated with occurrence and development of pituitary adenomas. Detecting CD151 might be a vital index to predict prognosis of pituitary adenomas.

Adenoma ; metabolism ; Blotting, Western ; Humans ; Immunohistochemistry ; Pituitary Gland ; pathology ; Pituitary Neoplasms ; metabolism ; Prognosis ; RNA, Messenger ; Real-Time Polymerase Chain Reaction ; Tetraspanin 24 ; metabolism

OBJECTIVETo investigate the effect of acupuncture on progesterone (P4) and prolactin (PRL) in rats of embryo implantation dysfunction (EID).

METHODSOn the first day of pregnancy, 72 female Wistar rats were randomly allocated into the normal group, the EID model group, the acupuncture group and the P4 group (18 in each group). The normal group was injected sesame oil, while the other three groups were given mifepristone to establish the EID model. The acupuncture group and the P4 group were given treatment of acupuncture and P4 injection, respectively. The serum of P4 and PRL were detected by radioimmunoassay, and the mRNA and protein expressions of P4 receptor (PR) and PRL receptor (PRLR) were detected using real-time polymerase chain reaction and immunohistochemical method, respectively.

RESULTSCompared with the normal group, the serum levels of P4 and PRL as well as the mRNA and protein expression levels of PR and PRLR in the EID model group were significantly lowered (P<0.01 or P<0.05). The above indices in the acupuncture group and the P4 group were significantly elevated compared with the EID model group (P<0.01 or P<0.05).

CONCLUSIONAcupuncture can promote embryo implantation effectively, which might be related to the effects of acupuncture on upregulating the P4 and PRL levels in serum and the PR and PRLR expression levels in rats.

Acupuncture Therapy ; Animals ; Embryo Implantation ; Endometrium ; metabolism ; Female ; Gene Expression Regulation ; Immunohistochemistry ; Male ; Pituitary Gland ; metabolism ; Pregnancy ; Progesterone ; blood ; Prolactin ; blood ; RNA, Messenger ; genetics ; metabolism ; Rats, Wistar ; Receptors, Progesterone ; genetics ; metabolism ; Receptors, Prolactin ; genetics ; metabolism

OBJECTIVETo compare changes of hypothalamus-pituitary-adrenal axis (HPAA) in different rat models of Gan stagnation (GS), Pi deficiency (PD), Gan stagnation Pi deficiency (GSPD) syndromes, and to observe interventional effect of Chaishu Sijun Decoction (CSD, capable of soothing Gan-qi invigorating Pi) on them.

METHODSSeventy Wistar rats were divided into the normal control group (group 1), the GS group (group 2), the PD group (group 3), the GSPD group (group 4), the GS intervention group (group 5), the PD intervention group (group 6), and the GSPD intervention group (group 7) according to random digit table, 10 in each group. Rats in group 1 received no treatment. Rats in group 2 and 5 were modeled by chronic restraint method. Rats in group 3 and 6 were modeled by excess fatigue plus alimentary abstinence method. Rats in group 4 and 7 were modeled by chronic restraint, excess fatigue, and alimentary abstinence method. At the 2nd weekend of modeling, CSD at 2.86 g/kg was fed to rats in group 5, 6, and 7 by gastrogavage for 2 successive weeks. Equal volume of distilled water was given to rats in the rest 4 groups. On the 29th day, rats were killed, adrenal weight weighed, and adrenal index calculated. Levels of plasma and hypothalamus corticotropin-releasing hormone (CRH), plasma and pituitary adrenocorticotrophic hormone (ACTH), and plasma corticosterone (CORT) were determined using radioimmunity.

RESULTSCompared with group 1, adrenal index significantly decreased in group 2, 3, and 4 (P < 0.05). Of them, plasma and hypothalamus CRH, plasma CORT increased significantly in group 2 and 4 (P < 0.05). Besides, plasma and pituitary ACTH increased in group 4 (P < 0.05). Plasma and pituitary ACTH, as well as plasma CORT decreased significantly in group 3 (P < 0.05). Compared with group 2, 3, and 4, adrenal index increased significantly in group 5, 6, and 7 (P < 0.05). Compared with group 2, plasma CORT, hypothalamus CRH, and pituitary ACTH decreased significantly in group 5 (P < 0.05). Compared with group 3, plasma ACTH and CORT increased significantly in group 6 (P < 0.05). Compared with group 4, plasma CRH, ACTH, CORT, hypothalamus CRH, and pituitary ACTH decreased in group 7 (P < 0.05).

CONCLUSIONSThe function of HPA .axis was damaged to varying degrees in rats of the three models in this experiment. Hyperactivity of HPA axis existed in GS syndrome and GSPD syndrome. Impairment of feedback regulation in hypothalamus and pituitary was accompanied in GSPD syndrome. Hypofunction of HPA axis existed in PDS. CSD, capable of soothing Gan-qi invigorating'Pi, showed improvement on disarranged HPAA, but with optimal effect on GSPD syndrome. CSD had higher correlation with GSPD syndrome.

Adrenocorticotropic Hormone ; metabolism ; Animals ; Corticosterone ; Corticotropin-Releasing Hormone ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hypothalamo-Hypophyseal System ; metabolism ; Hypothalamus ; metabolism ; Medicine, Chinese Traditional ; Models, Animal ; Pituitary Gland ; metabolism ; Pituitary-Adrenal System ; metabolism ; Rats ; Rats, Wistar