Introduction: Functioning gonadotroph adenomas, also known as follicle-stimulating hormone (FSH)-secreting pituitary adenomas (FSH-omas), are rare pituitary tumors characterized by the secretion of biologically active FSH. Unlike the more common clinically nonfunctioning gonadotroph adenomas, these tumors produce endocrine manifestations due to excessive FSH secretion. Clinical presentation may result from local mass effects such as headache, visual disturbances due to optic chiasmal compression, or from hormonal activity affecting reproductive function. The endocrine manifestations vary between males and females and can lead to diagnostic challenges. Cases: We report two patients with functioning gonadotroph adenomas presenting with distinct clinical manifestations. The first case involved a 23-year-old female who presented with secondary amenorrhea for 4 years, accompanied by personality changes. Abdominal ultrasound demonstrated bilaterally enlarged multicystic ovaries suggestive of ovarian hyperstimulation, which subsequently regressed postoperatively. Biochemical evaluation revealed inappropriately elevated FSH levels (3.5-fold increase), with suppressed luteinizing hormone (LH) and markedly elevated estradiol levels (11-fold increase). Pituitary magnetic resonance imaging (MRI) identified a large sellar–suprasellar mass with mass effect, consistent with a pituitary macroadenoma. The second case involved a 68-year-old male who presented with progressively worsening vision over 2 years. Hormonal evaluation demonstrated elevated FSH levels (4.5-fold increase), with relatively normal LH and low testosterone levels. Pituitary MRI revealed a sellar mass consistent with a pituitary adenoma. Both patients subsequently underwent pterional craniotomy with tumor debulking. Histopathological examination confirmed gonadotroph adenomas, with positive immunohistochemical staining for FSH. Conclusion Functioning gonadotroph adenomas are rare and may present with diverse clinical features related to gonadal hyperstimulation or mass effects. Early recognition of the characteristic hormonal profile and radiological findings is crucial for diagnosis and appropriate management. These cases highlight the importance of considering functioning gonadotroph adenoma in patients presenting with unexplained gonadal hyperstimulation or atypical reproductive hormonal profiles.
Gonadotrophs ; Adenoma

Introduction: Functioning gonadotroph adenomas (FGPAs) in males are rare and typically present with macroorchidism. In elderly patients, the presentation can be confounding. This case illustrates a unique scenario where a pituitary tumor masked the physiological decline of testosterone, maintaining the patient’s stamina despite Introduction testicular involution. Case: A 65-year-old male was referred for a pituitary macroadenoma (10.7 × 10.6 × 11.4 mm) following progressive headaches. Remarkably, the patient denied symptoms of andropause; his stamina, mood, and libido were wellpreserved. Investigations revealed elevated folliclestimulating hormone (15.42 mIU/mL) and luteinizing hormone (12.1 mIU/mL) with normal testosterone levels. Scrotal ultrasound showed bilateral testicular involution (right: 8.66 mL, left: 7.21 mL), contradicting the expected macroorchidism of FGPA. Although the patient felt his vision was normal, a confrontation test revealed temporal visual field defects, indicating chiasmatic compression. This case presents a striking clinical discordance where tumorinduced gonadotropin hypersecretion provided a supraphysiological drive to the involuting testes, maintaining testosterone levels and masking andropause. The primary indication for transsphenoidal surgery is the Introduction evidence of visual field defects. However, removing the adenoma will abruptly eliminate this “hormonal drive.” Postoperative management will focus on rigorous hormonal monitoring. Testosterone replacement therapy is not immediately indicated; rather, it will be carefully planned only if postoperative evaluations demonstrate a significant hormonal decline accompanied by symptomatic hypogonadism. This tailored approach ensures that the benefits of intervention outweigh the potential risks in an elderly patient. Conclusion In elderly patients, FGPAs can mask age-related hormonal decline. In this case, clinicians must treat the patient, not just the tumor. Anticipating a potential decline in postoperative stamina is as crucial as the surgery itself. Comprehensive hormonal evaluation and a personalized approach to therapy are essential to preserve quality of life after the “masking” effect is removed.
Male ; Andropause ; Gonadotrophs

Introduction: Pituitary macroadenomas may present with mass effects, hypopituitarism, or hormone hypersecretion. Hyperprolactinemia, resulting from a prolactin-secreting tumor or stalk compression, typically suppresses gonadotropins. Thus, elevated follicle-stimulating hormone (FSH) and luteinizing hormone (LH) with low testosterone in this context are unusual. We report a macroprolactinoma with a clinically non-functioning gonadotroph adenoma. Case: A 69-year-old male presented with acute giddiness and headache while in Vietnam. He reported reduced libido but no visual symptoms or galactorrhea. Examination showed no neurological deficits, normal visual fields, and secondary sexual characteristics; bilateral testes volume of 25 mL. Magnetic resonance imaging (MRI) brain revealed a 1.6 × 2.2 × 2.1 cm pituitary macroadenoma compressing the optic chiasm and pituitary stalk. Initial pituitary evaluation demonstrated hyperprolactinemia (prolactin >200 µg/L; normal 2.4–13.1), central hypothyroidism (T4 6.8 pmol/L [7.8–14.4], thyroid-stimulating hormone 2.3 mIU/L [0.38–5.3]), elevated FSH (21.5 IU/L [1.2–19.2]) and LH (191 IU/L [1.24–8.62]), low testosterone (8.88 nmol/L), normal insulin-like growth factor 1 (IGF-1) (68 µg/L [46.5–191.9]), and cortisol 237 nmol/L. Cabergoline was initiated at 0.25 mg twice weekly and titrated to 1 mg twice weekly over 4 months, alongside levothyroxine 25 µg daily. Repeated MRI brain 2 months after cabergoline initiation showed a persistent macroadenoma (1.7 × 2.2 × 2.2 cm) with bilateral cavernous sinus extension. Prolactin decreased to <170 µg/L, central hypothyroidism persisted; levothyroxine was optimized, and hydrocortisone was initiated. At the 5-month follow-up, prolactin further improved to 57 µg/L. Central hypothyroidism and borderline adrenal function persisted, requiring continued replacement therapy. Testosterone remained low-normal (10.2 nmol/L) despite elevated FSH (15.4 IU/L) and LH (92 IU/L). Followup MRI and hormonal reassessment were planned in May 2026. Conclusion Profoundly elevated prolactin level >200 µg/L and response to cabergoline reflect true prolactinoma rather than stalk effect. Persistently low testosterone with discordant high FSH/LH suggests a non-functioning gonadotroph component producing biologically inactive gonadotropins. Definitive diagnosis requires histopathological confirmation, while serial biochemical and radiological follow-up guides management and clarifies tumor subtype.
Gonadotrophs ; Hyperprolactinemia

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*

OBJECTIVE: To observe the regulatory effects of moxibustion at "Guanyuan" (CV4) on the synthesis of extragonadal estradiol (E₂) and the expression of estrogen receptor (ER) in ovariectomized rats, aiming to explore the mechanism of moxibustion treatment for perimenopausal syndrome. METHODS: Forty-eight SD female rats of SPF grade were randomly divided into a sham-operation group, a model group and a moxibustion group, with 16 rats in each group. The model group and the moxibustion group underwent bilateral ovariectomy by the back incision method. Ten days after surgery, moxibustion was applied at "Guanyuan" (CV4) in the moxibustion group, 30 min each time, once a day for 10 days. After intervention, in the 3 groups, the body mass and uterus weight were measured; the serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and E₂, as well as the skin and hypothalamus levels of E₂ were detected by ELISA; the mRNA expression of aromatase (P450arom) in the skin and hypothalamus was detected by real-time PCR; the expression of ERα and ERβ in the hypothalamus, skin, and uterus was observed by immunofluorescence staining, and the density of positive cells was calculated using the Aipathwell digital pathology image analysis software. RESULTS: Compared with the sham-operation group, the body mass was increased (P<0.01) and the uterus weight was decreased (P<0.001) in the model group. Compared with the model group, the body mass was decreased in the moxibustion group (P<0.01). Compared with the sham-operation group, in the model group, the serum, hypothalamus and skin levels of E₂ were decreased (P<0.01, P<0.05), while the serum levels of FSH and LH were increased (P<0.01); the expression of ERα and ERβ in the skin, hypothalamus and uterus was decreased (P<0.05, P<0.001). Compared with the model group, in the moxibustion group, the serum levels of E₂ and LH, as well as the hypothalamus and skin levels of E₂ were increased (P<0.05, P<0.01); the mRNA expression of P450arom, as well as the expression of ERα and ERβ in the skin and hypothalamus were increased (P<0.05). CONCLUSION Moxibustion at "Guanyuan" (CV4) reduces the body mass of ovariectomized rats by enhancing the synthesis of extragonadal E₂ and increasing the expression of ER in the skin and hypothalamus, yet it does not alleviate uterine atrophy.
Animals ; Female ; Moxibustion ; Rats ; Ovariectomy ; Acupuncture Points ; Rats, Sprague-Dawley ; Humans ; Receptors, Estrogen/genetics* ; Estrogens/metabolism* ; Estradiol/metabolism* ; Hypothalamus/metabolism* ; Follicle Stimulating Hormone/blood* ; Aromatase/genetics* ; Luteinizing Hormone/blood* ; Skin/metabolism*

Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory condition with chronic and relapsing manifestations and is characterized by a disturbance in the interplay between the intestinal microbiota, the gut, and the brain. The microbiota-gut-brain axis involves interactions among the nervous system, the neuroendocrine system, the gut microbiota, and the host immune system. Increasing published data indicate that psychological stress exacerbates the severity of IBD due to its negative effects on the microbiota-gut-brain axis, including alterations in the stress response of the hypothalamic-pituitary-adrenal (HPA) axis, the balance between the sympathetic nervous system and vagus nerves, the homeostasis of the intestinal flora and metabolites, and normal intestinal immunity and permeability. Although the current evidence is insufficient, psychotropic agents, psychotherapies, and interventions targeting the microbiota-gut-brain axis show the potential to improve symptoms and quality of life in IBD patients. Therefore, further studies that translate recent findings into therapeutic approaches that improve both physical and psychological well-being are needed.
Humans ; Inflammatory Bowel Diseases/metabolism* ; Stress, Psychological/microbiology* ; Gastrointestinal Microbiome/physiology* ; Brain/metabolism* ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Animals

The circadian rhythm regulates the 24-hour physiological and behavioral cycles through endogenous molecular clocks governed by core clock genes via the transcription-translation feedback loop (TTFL). In mammals, the suprachiasmatic nucleus (SCN) serves as the central pacemaker, coordinating the timing of physiological processes throughout the body by regulating clock genes such as CLOCK, BMAL1, PER, and CRY. The molecular clocks of peripheral tissues and cells are synchronized by the SCN through TTFLs to regulate metabolism, immunity, and energy homeostasis. Numerous studies indicate that circadian rhythm disruption is closely related to obesity, type 2 diabetes, metabolic syndrome and other diseases, and the mechanism involves the dysregulation of glucose and lipid metabolism, abnormal insulin signaling and low-grade inflammation. In recent years, small-molecule compounds targeting the core clock components such as CRY, REV-ERB, and ROR have been identified and shown potential to modulate metabolic diseases by stabilizing or inhibiting the activity of key clock proteins. This review summarizes the mechanisms and advances in these compounds, and explores the challenges and future directions for their clinical translation, providing insights for chronotherapy-based metabolic disease interventions.
Humans ; Metabolic Diseases/physiopathology* ; Animals ; Circadian Rhythm/physiology* ; Biological Clocks/drug effects* ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Suprachiasmatic Nucleus/physiology*

Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*

Based on the ultra performance liquid chromatography-quadrupole Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology, combined with related literature, databases, and reference material information, this study qualitatively analyzed the components of Dayuanyin in the tissue of rats after gavage and employed molecular docking technology to predict the rationality of the mechanism behind the antipyretic effect of the in vivo components in Dayuanyin. A total of 21, 26, 20, 21, 14, and 31 prototype components and 3, 16, 3, 7, 5, and 24 metabolites were identified from the heart, liver, spleen, lung, kidney, and hypothalamus of the rats, respectively, and the binding ability of key components and targets was further verified by molecular docking. The results showed that all components had good binding ability with targets. The established UPLC-Q-Exactive Orbitrap-MS could effectively and quickly identify the Dayuanyin components distributed in tissue and preliminarily identify their metabolites. Many components were identified in the hypothalamus, which suggested that the components delivered to the brain should be focused on in the study on Dayuanyin in the treatment of febrile diseases. The molecular docking technology was used to predict the rationality of the mechanism behind its antipyretic effect, which lays the foundation for the clarification of the material basis and action mechanism of Dayuanyin, the development of new preparations, and the prediction of quality markers.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Molecular Docking Simulation ; Male ; Antipyretics/metabolism* ; Rats, Sprague-Dawley ; Tissue Distribution ; Mass Spectrometry ; Chromatography, High Pressure Liquid ; Hypothalamus/metabolism*

Long-term spaceflight exposes astronauts to multiple extreme environmental factors, such as cosmic radiation, microgravity, social isolation, and circadian rhythm disruption, that markedly increase the risk of depressive symptoms, posing a direct threat to mental health and mission safety. However, the underlying biological mechanisms remain complex and incompletely understood. The potential mechanisms of spaceflight-induced depressive symptoms involve multiple domains, including alterations in brain structure and function, dysregulation of neurotransmitters and neurotrophic factors, oxidative stress, neuroinflammation, neuroendocrine system imbalance, and gut microbiota disturbances. Collectively, these changes may constitute the biological foundation of depressive in astronauts during spaceflight. Space-related stressors may increase the risk of depressive symptoms through several pathways: impairing hippocampal neuroplasticity, suppressing dopaminergic and serotonergic system function, reducing neurotrophic factor expression, triggering oxidative stress and inflammatory responses, activating the hypothalamic-pituitary-adrenal axis, and disrupting gut microbiota homeostasis. Future research should integrate advanced technologies such as brain-computer interfaces to develop individualized monitoring and intervention strategies, enabling real-time detection and effective prevention of depressive symptoms to safeguard astronauts' psychological well-being and mission safety.
Space Flight ; Humans ; Astronauts/psychology* ; Depression/physiopathology* ; Gastrointestinal Microbiome ; Weightlessness/adverse effects* ; Oxidative Stress ; Brain/physiopathology* ; Hypothalamo-Hypophyseal System ; Neuronal Plasticity ; Pituitary-Adrenal System