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*

Objective: To investigate the clinicopathological characteristics of plurihormonal PIT1-lineage pituitary neuroendocrine tumors. Methods: Forty-eight plurihormonal PIT1-lineage tumors were collected between January 2018 and April 2022 from the pathological database of Sanbo Brain Hospital, Capital Medical University. The related clinical and imaging data were retrieved. H&E, immunohistochemical and special stains were performed. Results: Out of the 48 plurihormonal PIT1-lineage tumors included, 13 cases were mature PIT1-lineage tumors and 35 cases were immature PIT1-lineage tumors. There were some obvious clinicopathological differences between the two groups. Clinically, the mature plurihormonal PIT1-lineage tumor mostly had endocrine symptoms due to increased hormone production, while a small number of immature PIT1-lineage tumors had endocrine symptoms accompanied by low-level increased serum pituitary hormone; patients with the immature PIT1-lineage tumors were younger than the mature PIT1-lineage tumors; the immature PIT1-lineage tumors were larger in size and more likely invasive in imaging. Histopathologically, the mature PIT1-lineage tumors were composed of large eosinophilic cells with high proportion of growth hormone expression, while the immature PIT1-lineage tumors consisted of chromophobe cells with a relatively higher expression of prolactin; the mature PIT1-lineage tumors had consistently diffuse cytoplasmic positive staining for keratin, while the immature PIT1-lineage tumors had various expression for keratin; the immature PIT1-lineage tumors showed more mitotic figures and higher Ki-67 proliferation index; in addition, 25.0% (12/48) of PIT1-positive plurihormonal tumors showed abnormal positive staining for gonadotropin hormones. There was no significant difference in the progression-free survival between the two groups (P=0.648) by Kaplan-Meier analysis. Conclusions: Plurihormonal PIT1-lineage tumor belongs to a rare type of PIT1-lineage pituitary neuroendocrine tumors, most of which are of immature lineage. Clinically increased symptoms owing to pituitary hormone secretion, histopathologically increased number of eosinophilic tumor cells with high proportion of growth hormone expression, diffusely cytoplasmic keratin staining and low proliferative activity can help differentiate the mature plurihormonal PIT1-lineage tumors from the immature PIT1-lineage tumors. The immature PIT1-lineage tumors have more complicated clinicopathological characteristics.
Humans ; Neuroendocrine Tumors ; Pituitary Neoplasms/pathology* ; Pituitary Hormones ; Growth Hormone/metabolism* ; Keratins

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*

BACKGROUND: Follicle-stimulating hormone (FSH), a gonadotropin secreted by the pituitary gland, is a representative secondary sex hormone and an important indicator of reproductive function. The effects of heavy metals such as lead, cadmium, and mercury on humans have been studied, but reports on their effects on sex hormone levels are lacking. Therefore, we investigated the relationship between heavy metal exposure and FSH levels in Korean men and postmenopausal women. METHODS: A total of 4,689 adults (2,763 men and 1,926 postmenopausal women aged 50 years or over) who participated in the Second Korean National Environmental Health Survey (2012–2014) were included. We compared differences in serum FSH levels by demographic characteristics using the t-test and analysis of variance. Multiple linear regression analysis was used to determine the relationship between the blood levels of lead and mercury and the urine cadmium level, and serum FSH levels. RESULTS: On multiple linear regression analysis, lead exposure was positively associated with serum FSH concentrations in postmenopausal women (β = 2.929, p = 0.019). However, we found no significant association between serum FSH concentration and blood lead and mercury levels, or urine cadmium level, in men. CONCLUSIONS: This study suggests that lead exposure can affect the FSH level in postmenopausal women. Further studies are needed to evaluate the effects of low-dose long-term exposure to heavy metals on sex hormones.
Adult ; Cadmium ; Environmental Health ; Female ; Follicle Stimulating Hormone ; Gonadal Steroid Hormones ; Gonadotropins ; Humans ; Linear Models ; Male ; Metals, Heavy ; Pituitary Gland

OBJECTIVETo analyze the correlation between pituitary stalk interruption syndrome (PSIS) and prokineticin receptor 2 (PROKR2) and prokineticin 2 (RROK2) mutations.

METHODSPROKR2 and RROK2 genotypes were identified by multiplex polymerase chain reaction analysis with exon-flanking primers and by automated sequencing techniques with peripheral blood DNA samples from 59 patients with PSIS.

RESULTSOf these 59 PSIS patients, 6 showed intragenic deletions at the PROKR2 locus. Of them, 5 patients exhibited intragenic subsititution of exon 2 (c.991G>A), and the remaining one patient exhibited intragenic subsititution of exon 2 (c.1057C>T). No PROK2 mutation was found in these PSIS patients.

CONCLUSIONPROKR2 may be the susceptibility gene of PSIS.

Exons ; Gastrointestinal Hormones ; Genotype ; Humans ; Mutation ; Neuropeptides ; Pituitary Diseases ; Receptors, G-Protein-Coupled ; Receptors, Peptide

Tuberculous meningitis is a well-known cause of hypothalamic pituitary dysfunction. However, deficiencies of anterior pituitary hormones may only become evident years after recovery because symptoms are of insidious-onset and nonspecific. Pituitary hormones are essential for normal growth and sexual development in childhood, and for maintenance of healthy body composition. In addition, pituitary hormones and vitamin D are important for cardiovascular and bone health. Although evidence of the relationship between hypovitaminosis D and hypopituitarism is limited, some studies suggested that the incidence of vitamin D deficiency increased in hypopituitarism. We describe herein an unusual case of hypopituitarism and severe hypovitaminosis D presenting as osteoporotic fracture after cured tuberculous meningitis.
Body Composition ; Hypopituitarism* ; Incidence ; Osteoporotic Fractures* ; Pituitary Hormones ; Pituitary Hormones, Anterior ; Sexual Development ; Tuberculosis, Meningeal* ; Vitamin D ; Vitamin D Deficiency

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*

Sheehan's syndrome (SS) is postpartum hypopituitarism caused by necrosis of the pituitary gland. The onset in most cases is several months or even years after the inciting delivery, so it is often unrecognized and not adequately treated. Because SS often evolves slowly, it is usually diagnosed late. We report a 47-year old woman with loss of consciousness. Fourteen years ago, she had postpartum hemorrhage with subsequent amenorrhea and failure to lactate. Laboratory investigation showed low blood sugar and serum sodium levels, amid normal cortisol and thyroid function tests. Magnetic resonance imaging (MRI) of the pituitary revealed an empty sella consistent with SS. The presentation of hypoglycemia and hyponatremia are less known complications of Sheehan's syndrome with only a few documented in case reports.

Human ; Female ; Middle Aged ; Amenorrhea ; Empty Sella Syndrome ; Hydrocortisone ; Hypoglycemia ; Hyponatremia ; Hypopituitarism ; Lactic Acid ; Magnetic Resonance Imaging ; Pituitary Diseases ; Pituitary Gland ; Postpartum Hemorrhage ; Thyroid Function Tests ; Unconsciousness ; Growth Hormone ; Hormones

OBJECTIVETo explore the change pattern of hypothalamic-pituitary-adrenal (HPA) axis and related neurotransmitters under simulated weightlessness.

METHODSA total of 40 clean-grade male Wistar rats were randomly divided into a normal group, a tail-suspension group, an electroacupuncture (EA) at Neiguan (PC 6) group, an EA at Sanyinjiao (SP 6) group, 10 rats in each group. Rats in the tail-suspension group, EA at "Neiguan" (PC 6) group and EA at "Sanyinjiao" (SP 6) group were treated with tail suspension to simulate weightlessness effect. Rats in the normal group were treated with normal diet. Rats in the tail-suspension group were treated with tail suspension for 28 d. During the time of tail suspension, rats in the EA at "Neiguan" (PC 6) group were treated with EA at "Neiguan" (PC 6), 30 min per treatment, once every two days for 14 treatments, while rats in the EA at "Sanyinjiao" (SP 6) group were treated with EA at "Sanyinjiao" (SP 6), 30 min per treatment, once every two days for 14 treatments. Samples were all collected after 4 weeks. The contents of corticotropin releasing hormone (CRH) , adrenocorticotropic hormone (ACTH), corticosterone (CORT) in as well as 5-hydroxy tryptamine (5-HT), dopamine (DA), norepinephrine (NE) were measured by using radioimmunoassay.

RESULTSCompared with the normal group, in the tail-suspension group the content of ACTH in pituitary was significantly decreased (P< 0.05), and the content of 5-HT in hypothalamus was significantly decreased (P < 0.01); the content of CRH and 5-HT in hypothalamus was significantly decreased (P < 0.01, P < 0.05) in the EA at "Neiguan" (PC 6) group; the content of CRH and 5-HT in hypothalamus was significantly decreased (P < 0.01), and the content of CORT in serum was significantly decreased (P < 0.05) in the EA at "Sanyinjiao" (SP 6) group. Compared with the tail-suspension group, the content of ACTH in hypothalamus was significantly decreased (P< 0.05) in the EA at "Neiguan" (PC 6) group; the content of CRH, ACTH and CORT was significantly decreased (P < 0.01, P < 0.05) in the EA at "Sanyinjiao" (SP 6) group. Compared with the EA at "Neiguan" (PC 6) group, the content of CORT was decreased (P < 0.05) in the EA at "Sanyinjiao" (SP 6) group.

CONCLUSIONEA can regulate the content of 5-HT in hypothalamus in tail-suspension rats, inhibit the hyperactivity of the HPA axis, in which EA at "Sanyinjiao" (SP 6) had more significant effects than "Neiguan" (PC 6), but no obvious effects on NE and DA were observed.

Acupuncture Points ; Adrenocorticotropic Hormone ; metabolism ; Animals ; Corticotropin-Releasing Hormone ; metabolism ; Dopamine ; metabolism ; Electroacupuncture ; Hormones ; metabolism ; Hypothalamus ; metabolism ; Male ; Neurotransmitter Agents ; metabolism ; Norepinephrine ; metabolism ; Pituitary-Adrenal System ; metabolism ; Rats ; Rats, Wistar ; Serotonin ; metabolism ; Weightlessness