A Neuro-hormonal Circuit for Paternal Behavior Controlled by a Hypothalamic Network Oscillation.

Parental behavior is pervasive throughout the animal kingdom and essential for species survival. However, the relative contribution of the father to offspring care differs markedly across animals, even between related species. The mechanisms that organize and control paternal behavior remain poorly understood. Using Sprague-Dawley rats and C57BL/6 mice, two species at opposite ends of the paternal spectrum, we identified that distinct electrical oscillation patterns in neuroendocrine dopamine neurons link to a chain of low dopamine release, high circulating prolactin, prolactin receptor-dependent activation of medial preoptic area galanin neurons, and paternal care behavior in male mice. In rats, the same parameters exhibit inverse profiles. Optogenetic manipulation of these rhythms in mice dramatically shifted serum prolactin and paternal behavior, whereas injecting prolactin into non-paternal rat sires triggered expression of parental care. These findings identify a frequency-tuned brain-endocrine-brain circuit that can act as a gain control system determining a species' parental strategy.

An analogue of the Prolactin Releasing Peptide reduces obesity and promotes adult neurogenesis.

Hypothalamic Adult Neurogenesis (hAN) has been implicated in regulating energy homeostasis. Adult-generated neurons and adult Neural Stem Cells (aNSCs) in the hypothalamus control food intake and body weight. Conversely, diet-induced obesity (DIO) by high fat diets (HFD) exerts adverse influence on hAN. However, the effects of anti-obesity compounds on hAN are not known. To address this, we administered a lipidized analogue of an anti-obesity neuropeptide, Prolactin Releasing Peptide (PrRP), so-called LiPR, to mice. In the HFD context, LiPR rescued the survival of adult-born hypothalamic neurons and increased the number of aNSCs by reducing their activation. LiPR also rescued the reduction of immature hippocampal neurons and modulated calcium dynamics in iPSC-derived human neurons. In addition, some of these neurogenic effects were exerted by another anti-obesity compound, Liraglutide. These results show for the first time that anti-obesity neuropeptides influence adult neurogenesis and suggest that the neurogenic process can serve as a target of anti-obesity pharmacotherapy.

Establishment and characterization of equine mammary organoids using a method translatable to other non-traditional model species.

Mammary organoid (MaO) models are only available for a few traditional model organisms, limiting our ability to investigate mammary gland development and cancer across mammals. This study established equine mammary organoids (EqMaOs) from cryopreserved mammary tissue, in which mammary tissue fragments were isolated and embedded into a 3D matrix to produce EqMaOs. We evaluated viability, proliferation and budding capacity of EqMaOs at different time points during culture, showing that although the number of proliferative cells decreased over time, viability was maintained and budding increased. We further characterized EqMaOs based on expression of stem cell, myoepithelial and luminal markers, and found that EqMaOs expressed these markers throughout culture and that a bilayered structure as seen in vivo was recapitulated. We used the milk-stimulating hormone prolactin to induce milk production, which was verified by the upregulation of milk proteins, most notably ß-casein. Additionally, we showed that our method is also applicable to additional non-traditional mammalian species, particularly domesticated animals such as cats, pigs and rabbits. Collectively, MaO models across species will be a useful tool for comparative developmental and cancer studies.

Nociceptors are functionally male or female: from mouse to monkey to man.

The prevalence of many pain conditions often differs between sexes. In addition to such quantitative distinctions, sexual dimorphism may also be qualitative reflecting differences in mechanisms that promote pain in men and women. A major factor that influences the likelihood of pain perception is the threshold for activation of nociceptors. Peripheral nociceptor sensitization has been demonstrated to be clinically relevant in many pain conditions. Whether peripheral nociceptor sensitization can occur in a sexually dimorphic fashion, however, has not been extensively studied. To address this fundamental knowledge gap, we used patch clamp electrophysiology to evaluate the excitability of dorsal root ganglion neurones from male or female rodents, non-human primates, and humans following exposure to putative sensitizing agents. Previous studies from our laboratory, and others, have shown that prolactin promotes female-selective pain responses in rodents. Consistent with these observations, dorsal root ganglion neurones from female, but not male, mice were selectively sensitized by exposure to prolactin. The sensitizing action of prolactin was also confirmed in dorsal root ganglion neurones from a female macaque monkey. Critically, neurones recovered from female, but not male, human donors were also selectively sensitized by prolactin. In the course of studies of sleep and pain, we unexpectedly observed that an orexin antagonist could normalize pain responses in male animals. We found that orexin B produced sensitization of male, but not female, mouse, macaque, and human dorsal root ganglion neurones. Consistent with functional responses, increased prolactin receptor and orexin receptor 2 expression was observed in female and male mouse dorsal root ganglia, respectively. Immunohistochemical interrogation of cultured human sensory neurones and whole dorsal root ganglia also suggested increased prolactin receptor expression in females and orexin receptor 2 expression in males. These data reveal a functional double dissociation of nociceptor sensitization by sex, which is conserved across species and is likely directly relevant to human pain conditions. To our knowledge, this is the first demonstration of functional sexual dimorphism in human sensory neurones. Patient sex is currently not a common consideration for the choice of pain therapy. Precision medicine, based on patient sex could improve therapeutic outcomes by selectively targeting mechanisms promoting pain in women or men. Additional implications of these findings are that the design of clinical trials for pain therapies should consider the proportions of male or female patients enrolled. Lastly, re-examination of selected past failed clinical trials with subgroup analysis by sex may be warranted.

Prolactin-mediated restraint of maternal aggression in lactation.

Aggressive behavior is rarely observed in virgin female mice but is specifically triggered in lactation where it facilitates protection of offspring. Recent studies demonstrated that the hypothalamic ventromedial nucleus (VMN) plays an important role in facilitating aggressive behavior in both sexes. Here, we demonstrate a role for the pituitary hormone, prolactin, acting through the prolactin receptor in the VMN to control the intensity of aggressive behavior exclusively during lactation. Prolactin receptor deletion from glutamatergic neurons or specifically from the VMN resulted in hyperaggressive lactating females, with a marked shift from intruder-directed investigative behavior to very high levels of aggressive behavior. Prolactin-sensitive neurons in the VMN project to a wide range of other hypothalamic and extrahypothalamic regions, including the medial preoptic area, paraventricular nucleus, and bed nucleus of the stria terminalis, all regions known to be part of a complex neuronal network controlling maternal behavior. Within this network, prolactin acts in the VMN to specifically restrain male-directed aggressive behavior in lactating females. This action in the VMN may complement the role of prolactin in other brain regions, by shifting the balance of maternal behaviors from defense-related activities to more pup-directed behaviors necessary for nurturing offspring.

Discovery of prolactin-like in lamprey: Role in osmoregulation and new insight into the evolution of the growth hormone/prolactin family.

We used a representative of one of the oldest extant vertebrate lineages (jawless fish or agnathans) to investigate the early evolution and function of the growth hormone (GH)/prolactin (PRL) family. We identified a second member of the GH/PRL family in an agnathan, the sea lamprey (Petromyzon marinus). Structural, phylogenetic, and synteny analyses supported the identification of this hormone as prolactin-like (PRL-L), which has led to added insight into the evolution of the GH/PRL family. At least two ancestral genes were present in early vertebrates, which gave rise to distinct GH and PRL-L genes in lamprey. A series of gene duplications, gene losses, and chromosomal rearrangements account for the diversity of GH/PRL-family members in jawed vertebrates. Lamprey PRL-L is produced in the proximal pars distalis of the pituitary and is preferentially bound by the lamprey PRL receptor, whereas lamprey GH is preferentially bound by the lamprey GH receptor. Pituitary PRL-L messenger RNA (mRNA) levels were low in larvae, then increased significantly in mid-metamorphic transformers (stage 3); thereafter, levels subsided in final-stage transformers and metamorphosed juveniles. The abundance of PRL-L mRNA and immunoreactive protein increased in the pituitary of juveniles under hypoosmotic conditions, and treatment with PRL-L blocked seawater-associated inhibition of freshwater ion transporters. These findings clarify the origin and divergence of GH/PRL family genes in early vertebrates and reveal a function of PRL-L in osmoregulation of sea lamprey, comparable to a role of PRLs that is conserved in jawed vertebrates.

Neuregulin 4 (Nrg4) cooperates with melatonin to regulate the PRL expression via ErbB4/Erk signaling pathway as a potential prolactin (PRL) regulator.

Neuregulin-4 (Nrg4) and melatonin play vital roles in endocrine diseases. However, there is little discussion about the function and potential mechanism of Nrg4 and melatonin in prolactin (PRL) regulation. The human normal pituitary data from Gene Expression Profiling Interactive Analysis (GEPIA) database was used to explore the correlation between NRG4 and PRL. The expression and correlation of NRG4 and PRL were determined by Immunofluorescence staining (IF) and human normal pituitary tissue microarray. Western Blot (WB) was used to detect the expression of PRL, p-ErbB2/3/4, ErbB2/3/4, p-Erk1/2, Erk1/2, p-Akt and Akt in PRL-secreting pituitary GH3 and RC-4B/C cells treated by Nrg4, Nrg4-small interfering RNA, Erk1/2 inhibitor FR180204 and melatonin. The expression of NRG4 was significantly positively correlated with that of PRL in the GEPIA database and normal human pituitary tissues. Nrg4 significantly increased the expression and secretion of PRL and p-Erk1/2 expression in GH3 cells and RC-4B/C cells. Inhibition of Nrg4 significantly inhibited PRL expression. The increased levels of p-Erk1/2 and PRL induced by Nrg4 were abolished significantly in response to FR180204 in GH3 and RC-4B/C cells. Additionally, Melatonin promotes the expression of Nrg4, p-ErbB4, p-Erk1/2, and PRL and can further promote the expression of p-Erk1/2 and PRL in combination with Nrg4. Further investigation into the function of Nrg4 and melatonin on PRL expression and secretion may provide new clues to advance the clinical control of prolactinomas and hyperprolactinemia.

Follow-Up Study of 17-ß Estradiol, Prolactin and Progesterone with the Kinetics and Prevalence of T. gondii Infection in Pregnant Women.

Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. One-third of the world's population has come into contact with this parasite. In Mexico, the prevalence is between 15% and 50% in the general population and 34.9% in women with high-risk pregnancies. In pregnancy, the highest incidence of infection occurs in the third trimester and fetal damage is inversely proportional to gestational age. Maternal hormones play a fundamental role in the immune response. There are very few studies, with controversial results, on the levels of increased hormones and their relationship to the kinetics of T. gondii infections during pregnancy. The aim was to determine the serum levels of 17-ß estradiol, prolactin, and progesterone, and their association with anti-T. gondii antibodies' kinetics in pregnancy. Fifty-two pregnant patients were studied. A questionnaire with sociodemographic and clinical aspects was used. Afterward, 10 mL of venous blood was collected by venipuncture every trimester. The concentrations of 17-ß estradiol, progesterone, and prolactin were measured, using the ELISA method. In addition, anti-Toxoplasma IgG and IgM antibodies were also determined in the first, second, and third trimester. The prevalence of anti-Toxoplasma IgG antibodies was 26.92% in the first and second trimester and 32.7% in the third trimester. In seropositive women, 17-ß estradiol increased in the second and third trimesters of pregnancy. Progesterone increased significantly p < 0.039 in the third trimester in these women, while prolactin increased in the second trimester with a statistical significance of p < 0.021. In addition, 17-ß estradiol, progesterone, and prolactin are associated with T. gondii infection during pregnancy. New studies are necessary to clarify the specific mechanisms of immune response related to these hormones during pregnancy.

The dissection of a despotic society: exploration, dominance and hormonal traits.

Naked mole-rats (Heterocephalus glaber) live in large colonies with one breeding female (queen), one to three breeding males (BMs) and the remainder are non-reproductive subordinates. The animals have a linear dominance rank with the breeders at the top of the hierarchy. We investigated how dominance rank in naked mole-rats differs with exploration (the propensity to explore a novel environment) and related endocrine markers. Exploration behaviour, faecal progestagen metabolite (fPM), faecal glucocorticoid metabolite (fGCM), faecal androgen metabolite (fAM) and plasma prolactin concentrations were quantified in breeding, high-, middle- and low-ranked females and males from five naked mole-rat colonies. There were no significant differences between the dominance rank and exploration behaviour. Interestingly, the queens and high-ranking females had higher fGCM and fAM concentrations compared with middle- and low-ranked females. The queens had significantly higher fPM concentrations than all other ranked females, since they are responsible for procreation. In the males, the BMs had higher fGCM concentrations compared with high- and low-ranked males. In addition, BMs and middle-ranking males had overall higher prolactin levels than all other ranked males, which could be linked to cooperative care. Overall, the results suggest that physiological reproductive suppression is linked to high dominance rank.

Macroprolactin over time: Is there any point in rechecking it in people with a persistently elevated serum prolactin?

OBJECTIVE AND DESIGN: Macroprolactinemia may influence the interpretation of serum prolactin levels-a recognised phenomenon since 1981. The degree of macroprolactinaemia over time is less well described. We determined how macroprolactin status (based on polyethylene glycol (PEG) precipitation) varied by analysing serial measurements in hyperprolactinaemic individuals over a period of 9 years. PATIENTS AND MEASUREMENTS: Results from 1810 individuals were included. All serum total prolactin results (measured using Roche Cobas 8000 analyser) were extracted from the laboratory information system for the period 1 January 2012 to 1 April 2021, along with relevant patient demographic/test data. Samples with a macroprolactin screening test performed (on samples with prolactin > 700 miu/L) were included in the main analysis. RESULTS: During the study period, 2782 macroprolactin checks were performed (12.5% of all prolactin tests) in 1810 individuals (599 males/2183 females, median-age: 35, interquartile range: 25-47, range: 16-93 years). Multiple macroprolactin checks were carried out on 465 patients (1437 measurements) with 94 patients (141 measurements) screening positive (<60% recovery). Only 19 patients (18 female) had at least one result above and one below the 60% screening cut-off, with 10 of these patients having results close to the 60% cut-off; in 9 patients, results were clearly different between repeat samples. In seven cases, the adjusted monomeric prolactin showed a potentially clinically significant difference. CONCLUSIONS: In this study, only 19/465 patients appeared to change macroprolactin status based on a 60% PEG recovery cut-off. The majority of these 19 patients were on antipsychotic/antidepressant medication(s) or had a prolactinoma; in only 7 did monomeric prolactin change significantly. This suggests that once macroprolactin status has been determined, clinical decision making is rarely affected by repeating it.

Prolactin effects on the pathogenesis of diabetes mellitus.

BACKGROUND: Prolactin (PRL) is a pituitary hormone promoting lactation in response to the suckling reflex. Beyond its well-known effects, novel tissue-specific and metabolic functions of PRL are emerging. AIMS: To dissect PRL as a critical mediator of whole-body gluco-insulinemic sensitivity. METHODS: PubMed-based search with the following terms 'prolactin', 'glucose metabolism', 'type 2 diabetes mellitus', 'type 1 diabetes mellitus', 'gestational diabetes mellitus' was performed. DISCUSSION: The identification of the PRL-glucose metabolism network poses the basis for unprecedented avenues of research in the pathogenesis of diabetes mellitus type 1 or 2, as well as of gestational diabetes. In this regard, it is of timely relevance to define properly the homeostatic PRL serum levels since glucose metabolism could be influenced by the circulating amount of the hormone. RESULTS: This review underscores the basic mechanisms of regulation of pancreatic ß-cell functions by PRL and provides a revision of articles which have investigated the connection between PRL unbalancing and diabetes mellitus. Future studies are needed to elucidate the burden and the role of PRL in the regulation of glucose metabolism and determine the specific PRL threshold that may impact the management of diabetes. CONCLUSION: A careful evaluation and context-driven interpretation of PRL levels (e.g., pregnancy, PRL-secreting pituitary adenomas, drug-related hyper- and hypoprolactinemia) could be critical for the correct screening and management of glucometabolic disorders, such as type 1 or 2 as well as gestational diabetes mellitus.

Sleep promotes T-cell migration towards CCL19 via growth hormone and prolactin signaling in humans.

Sleep strongly supports the formation of adaptive immunity, e.g., after vaccination. However, the underlying mechanisms remain largely obscure. Here we show in healthy humans that sleep compared to nocturnal wakefulness specifically promotes the migration of various T-cell subsets towards the chemokine CCL19, which is essential for lymph-node homing and, thus, for the initiation and maintenance of adaptive immune responses. Migration towards the inflammatory chemokine CCL5 remained unaffected. Incubating the cells with plasma from sleeping participants likewise increased CCL19-directed migration, an effect that was dependent on growth hormone and prolactin signaling. These findings show that sleep selectively promotes the lymph node homing potential of T cells by increasing hormonal release, and thus reveal a causal mechanism underlying the supporting effect of sleep on adaptive immunity in humans.

Prolactin promotes the recruitment of main olfactory bulb cells and enhances the behavioral exploration toward a socio-sexual stimulus in female mice.

Olfactory communication is triggered by pheromones that profoundly influence neuroendocrine responses to drive social interactions. Two principal olfactory systems process pheromones: the main and the vomeronasal or accessory system. Prolactin receptors are expressed in both systems suggesting a participation in the processing of olfactory information. We previously reported that prolactin participates in the sexual and olfactory bulb maturation of females. Therefore, we explored the expression of prolactin receptors within the olfactory bulb during sexual maturation and the direct responses of prolactin upon pheromonal exposure. Additionally, we assessed the behavioral response of adult females exposed to male sawdust after prolactin administration and the consequent activation of main and accessory olfactory bulb and their first central relays, the piriform cortex and the medial amygdala. Last, we investigated the intracellular pathway activated by prolactin within the olfactory bulb. Here, prolactin receptor expression remained constant during all maturation stages within the main olfactory bulb but decreased in adulthood in the accessory olfactory bulb. Behaviorally, females that received prolactin actively explored the male stimulus. An increased cFos activation in the amygdala and in the glomerular cells of the whole olfactory bulb was observed, but an augmented response in the mitral cells was only found within the main olfactory bulb after prolactin administration and the exposure to male stimulus. Interestingly, the ERK pathway was upregulated in the main olfactory bulb after exposure to a male stimulus. Overall, our results suggest that, in female mice, prolactin participates in the processing of chemosignals and behavioral responses by activating the main olfactory system and diminishing the classical vomeronasal response to pheromones.

Prolactin is associated with proximity to incubating partner rather than parental care in black-headed gulls.

The peptide hormone prolactin plays an important role in the expression of parental care behaviours across bird and mammal taxa. While a great deal is known about how plasma prolactin concentrations vary across the reproductive cycle, the few studies that investigate how prolactin relates to individual-level variation in parental care have reported mixed results. We argue that, since parental care is also affected by social interactions and environmental constraints, prolactin may better reflect behaviours that are indirectly related to parenting than the absolute level of care that is eventually expressed. In this study, we tested for associations between plasma prolactin and the expression of both parental care and proximity to the partner in incubating black-headed gulls, Chroicocephalus ridibundus. Baseline prolactin levels increased with calendar date but were unrelated to incubation behaviours. However, parents who showed a weaker decrease in prolactin to an acute stressor spent more time in close proximity to their incubating partner while not on the nest themselves, suggesting that individual variation in stress-induced prolactin changes reflect differences in parents' tendency to be closely associated with their partner and the joint nesting attempt. Baseline and stress-induced levels of the stress hormone corticosterone were unrelated to both prolactin levels and parental behaviours, suggesting that this hormone is not a strong moderator of parental care in black-headed gulls. One potential explanation for the link between prolactin dynamics and partner proximity is that prolactin reflects parental motivation to provide parental care or retain contact with the breeding partner, but further work is needed to directly test this hypothesis.

Prolactin is an Endogenous Antioxidant Factor in Astrocytes That Limits Oxidative Stress-Induced Astrocytic Cell Death via the STAT3/NRF2 Signaling Pathway.

Oxidative stress-induced death of neurons and astrocytes contributes to the pathogenesis of numerous neurodegenerative diseases. While significant progress has been made in identifying neuroprotective molecules against neuronal oxidative damage, little is known about their counterparts for astrocytes. Prolactin (PRL), a hormone known to stimulate astroglial proliferation, viability, and cytokine expression, exhibits antioxidant effects in neurons. However, its role in protecting astrocytes from oxidative stress remains unexplored. Here, we investigated the effect of PRL against hydrogen peroxide (H2O2)-induced oxidative insult in primary cortical astrocyte cultures. Incubation of astrocytes with PRL led to increased enzymatic activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX), resulting in higher total antioxidant capacity. Concomitantly, PRL prevented H2O2-induced cell death, reactive oxygen species accumulation, and protein and lipid oxidation. The protective effect of PRL upon H2O2-induced cell death can be explained by the activation of both signal transducer and activator of transcription 3 (STAT3) and NFE2 like bZIP transcription factor 2 (NRF2) transduction cascades. We demonstrated that PRL induced nuclear translocation and transcriptional upregulation of Nrf2, concurrently with the transcriptional upregulation of the NRF2-dependent genes heme oxygenase 1, Sod1, Sod2, and Gpx1. Pharmacological blockade of STAT3 suppressed PRL-induced transcriptional upregulation of Nrf2, Sod1 and Gpx1 mRNA, and SOD and GPX activities. Furthermore, genetic ablation of the PRL receptor increased astroglial susceptibility to H2O2-induced cell death and superoxide accumulation, while diminishing their intrinsic antioxidant capacity. Overall, these findings unveil PRL as a potent antioxidant hormone that protects astrocytes from oxidative insult, which may contribute to brain neuroprotection.

Wheel Running During Pregnancy Alleviates Anxiety-and Depression-Like Behaviors During the Postpartum Period in Mice: The Roles of NLRP3 Neuroinflammasome Activation, Prolactin, and the Prolactin Receptor in the Hippocampus.

Despite the increase in the prevalence of postpartum depression among maternal disorder, its treatment outcomes remain suboptimal. Studies have shown that exercise can reduce postpartum depressive episodes in the mother, but the effects of exercise during pregnancy on maternal behavior and the potential mechanisms involved remain poorly understood. From the second day of pregnancy to the day of birth, dams exercised for 1 h a day by running on a controlled wheel. The maternal behaviors of the dams were assessed on postpartum day 2 to postpartum day 8. Chronic restraint stress was applied from postpartum day 2 to day 12. Blood was collected on postpartum days 3 and 8, then subjected to ELISA to determine the serum concentration of prolactin. The weight of each dam and the food intake were recorded. Anxiety- and depression-like behavioral tests were conducted, and hippocampal neuroinflammation and prolactin receptor levels were measured. The dams exhibited elevated levels of anxiety and depression, decreased serum prolactin levels, decreased prolactin receptor expression, and activation of NLRP3-mediated neuroinflammation in the hippocampus following the induction of postpartum chronic restraint stress, which were reversed with controlled wheel running during pregnancy. Overall, the findings of this study revealed that the preventive effects of exercise during pregnancy on postpartum anxiety-and depression-like behaviors were accompanied by increased serum prolactin levels, hippocampal prolactin receptor expression and hippocampal NLRP3-mediated neuroinflammation.

The relationship between serum prolactin levels and cognitive function in drug-naïve schizophrenia patients: a cross-sectional study.

This study aimed to investigate the association between serum prolactin levels and psychiatric symptoms and cognitive function in drug-naïve schizophrenia patients. The study recruited 91 drug-naïve schizophrenia patients and 67 healthy controls. Sociodemographic and clinical data were collected, and cognitive function was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). Serum prolactin levels were measured, and statistical analyses were performed to examine the relationship between prolactin levels, clinical symptoms, and cognitive function. The study found that drug-naïve schizophrenia patients had severe cognitive deficits compared to healthy controls across all seven domains of the MCCB. However, no correlation was found between these patients' serum prolactin levels and clinical severity or cognitive function. The drug-naïve schizophrenia patients had significant cognitive deficits compared to healthy controls. However, there was no significant relationship between prolactin levels and symptomatology and cognition in drug-naïve schizophrenia patients.

Simultaneous Detection of Prolactin and Growth Hormone Using a Dual-label Time-resolved Fluorescence Immunoassay.

Prolactin (PRL) and growth hormone (GH) are two important hormones secreted by the pituitary gland, and their abnormal levels are often related to disease status. This study aimed to establish a new dual-label time-resolved fluorescence immunoassay (TRFIA) to quantitatively measure PRL and GH levels in serum. A sandwich TRFIA was optimized and established: anti-PRL/GH antibodies immobilized on 96-well plates captured PRL/GH and then banded together with anti-PRL/GH paired antibodies labeled with europium(III) (Eu3+)/samarium(III) (Sm3+) chelates. Finally, a time-resolved analyzer measured the Eu3+/Sm3+ fluorescence values. Clinical serum samples were used to evaluate the detection performance of this method. The sensitivities of this dual-label TRFIA were 0.35 ng/mL and 0.45 ng/mL, respectively, and the detection range was between 0.1 and 1000 ng/mL. All the cross-reactivities were lower than 1.07%. The intra-assay and interassay coefficients of variation were 2.18-7.85% and 2.25-7.30%, respectively. Compared with the registered TRFIA kits, a high Pearson coefficient (r = 0.9626 and 0.9675) was observed. This dual-label TRFIA has high sensitivity, accuracy and specificity with good clinical detection performance, representing a suitable alternative to existing methods for determining PRL and GH levels, and is expected to be used in the clinic in the future.

The diagnosis and prevalence of hypoprolactinemia in patients with panhypopituitarism and the effects on depression and sexual functions.

PURPOSE: We aimed to investigate the prevalence and the diagnostic criteria of hypoprolactinemia in patients with panhypopituitarism and the effects of hypoprolactinemia on depression and sexual functions. MATERIALS AND METHODS: Forty-eight patients with panhypopituitarism and 20 healthy volunteers were included. Basal hormone levels were measured and a TRH stimulation test was performed. For the evaluation of sexual functions, questionnaries of Female Sexual Functional Index (FSFI) for females and International Erectile Functional Index for males were performed to the subjects. Depressive symptoms were evaluated by Beck Depression Envontory score (BDI-II). RESULTS: The peak PRL response to TRH stimulation test at 5th percentile in the control group was 18.6 ng/ml in males and 41.6 ng/ml in females and accepted as the cut-offs for sufficient response of PRL. Prolactin was insufficient in 42(87.5%) patients. A basal PRL level of ≤ 5.7 ng/ml in males and 7.11 ng/ml in females was 100% specific in predicting an inadequate response to TRH stimulation test with 80% and 70% sensitivity respectively. A basal PRL level of ≥ 8.5 ng/dl in males was 100% specific and 76% sensitive, and in females a level of ≥ 15.2 ng/dl was 96% specific and 66% sensitive in predicting an adequate response to TRH. PRL deficient patients with panhypopituitarism had higher depression scores compared to the controls, lower sexual function scores in males. CONCLUSION: PRL deficiency is prevalent among individuals with panhypopituitarism, with the potential to result in elevated depression scores in both sexes and impaired sexual functions in males. A basal PRL level seems to be sufficient for the diagnosis of hypoprolactinemia in routine clinical practice.

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.