Role Of Prolactin Research Articles

Peripartum prolactin and cortisol level changes. A prospective pilot study.

Although the role of prolactin and cortisol in the human lactation process seems to be undisputed, the changes in postpartum serum concentrations in mothers make data interpretation difficult. To determine the factors that possibly influence these hormones, we examined a group of patients who were admitted to the Gynecology-Obstetrics Clinical Hospital in Poznań for labor induction and/or in the active phase of the first labor period. The serum levels of cortisol and prolactin were assessed in these full-term pregnant women during admission to labor, in the third stage of labor, and on the second day postpartum. The prolactin and cortisol levels were also measured in the umbilical cord for the assessment of newborn babies. The results showed a significant relationship between maternal age and the level of prolactin measured before childbirth and fluctuations in cortisol level with respect to labor duration. In addition, we observed a strong correlation between the level of prolactin assessed before childbirth and the pH and base excess of the umbilical cord artery. Most importantly, a correlation was noted between breastfeeding within 2 hours after the labor and the level of cortisol measured after childbirth. We observed a significant correlation between a summarized labor duration and maternal and umbilical cord cortisol levels measured right after the labor. The fact of breastfeeding within 2 hours after the labor strongly correlated with lower levels of maternal cortisol as well as a cortisol level in umbilical cord blood and it suggests that immediate initiation of breastfeeding reduces stress level for both, mother and newborn.

The beneficial metabolic actions of prolactin.

The role of prolactin (PRL) favoring metabolic homeostasis is supported by multiple preclinical and clinical studies. PRL levels are key to explaining the direction of its actions. In contrast with the negative outcomes associated with very high (>100 μg/L) and very low (<7 μg/L) PRL levels, moderately high PRL levels, both within but also above the classically considered physiological range are beneficial for metabolism and have been defined as HomeoFIT-PRL. In animal models, HomeoFIT-PRL levels counteract insulin resistance, glucose intolerance, adipose tissue hypertrophy and fatty liver; and in humans associate with reduced prevalence of insulin resistance, fatty liver, glucose intolerance, metabolic syndrome, reduced adipocyte hypertrophy, and protection from type 2 diabetes development. The beneficial actions of PRL can be explained by its positive effects on main metabolic organs including the pancreas, liver, adipose tissue, and hypothalamus. Here, we briefly review work supporting PRL as a promoter of metabolic homeostasis in rodents and humans, the PRL levels associated with metabolic protection, and the proposed mechanisms involved. Finally, we discuss the possibility of using drugs elevating PRL for the treatment of metabolic diseases.

Low Prolactin Levels Identify HSDD and a Low Inhibition Profile in Women with Sexual Symptoms

ABSTRACT Introduction Data on the role of prolactin (PRL) in the physiologic range in the female sexual response are scanty. Objective We aimed at investigating the association between PRL levels and sexual function, and specifically, with the desire domain as assessed by the Female Sexual Function Index. We also explored the presence of a cut-off level of PRL able to identify women with a diagnosis of Hypoactive Sexual Desire Disorder (HSDD). Methods N=234 pre- and post-menopausal women (mean age 45.2+-12.4 years) consulting for female sexual dysfunction (FSD), and sexually active in the previous 4 weeks, were retrospectively analysed. A clinical, biochemical and pharmacological evaluation was performed. All patients completed the FSFI, the Female Sexual Distress Scale-Revised (FSDS-R), the Middlesex Hospital Questionnaire (MHQ) for the screening of psychopathological symptoms and the Sexual excitation/sexual inhibition scale (SIS/SES). Biochemical assessment included PRL (by luminescent oxygen channeling immunoassay). Results Only few patients (n=9) had hyperPRL (PRL&amp;gt; 483.0 mU/L) and showed a significantly higher MHQ total score (p=0.043), lower Total (p=0.037), Desire (p=0.002), Arousal (p=0.024) and Satisfaction (p=0.026) FSFI scores and a higher FSDS-R score (p=0.006) compared with women with normoPRL women. At univariate linear regression analysis, we did not find a significant correlation between FSFI total score and PRL levels. Hypothesizing the non-linearity of the association between these 2 variables, we tested different fitting models and found that the quadratic relationship was the best fitting (R2=0.11).When stratifying normoPRL women into tertiles (T1: PRL &amp;lt; 163.55 mU/L; T2= PRL &amp;gt; 163.55 and &amp;lt; 262.0 mU/L; T3: PRL &amp;gt; 262.0 and &amp;lt; 483.0 mU/L), a significant difference emerged in FSFI Desire (p=0.001), Arousal (p=0.033) and Satisfaction (p=0.019) among the 4 groups; however, only the difference in Desire was confirmed (p=0.034) in a multivariate model. A post-hoc analysis showed that only women in the T3 PRL tertile had significantly higher scores in FSFI Desire (p=0.011) and Satisfaction (0.045) vs. women with hyperPRL.After excluding hyperPRL women, we compared PRL between women with (n=35) and without HSDD (n=190) and observed that those with HSDD showed significantly lower PRL levels (p=0.002). ROC curve analysis for PRL levels showed an accuracy of 0.615 +- 0.022, p = 0.040, in predicting HSDD, and when a threshold of PRL&amp;lt;190 mU/L was chosen, sensitivity and specificity for HSDD were both 64.7%. Finally, we compared women with PRL levels &amp;gt; and &amp;lt; 190 mU/L. At multivariate analysis, women with PRL &amp;lt;190 mU/L showed a significantly lower cortisol (p=0.017) and SIS1 score (p=0.049), a scale of sexual inhibition, than women with PRL &amp;gt;190 mU/L (bit still in the normal range). Conclusions FSD women with hyperPRL showed a worse sexual function than those with normal PRL levels. However, when stratifying normoPRL women based on PRL tertiles, those included in the highest group had the best FSFI profile. Measuring PRL level in women with FSD is important, not only in order to ascertain the presence of a hyperPRL condition, but also to potentially predict the presence of HSDD or of a lower sexual inhibitory trait. Disclosure No

Prolactin and Maternal Metabolism in Women With a Recent GDM Pregnancy and Links to Future T2D: The SWIFT Study.

Prolactin is a multifaceted hormone known to regulate lactation. In women with gestational diabetes mellitus (GDM) history, intensive lactation has been associated with lower relative risk of future type 2 diabetes (T2D). However, the role of prolactin in T2D development and maternal metabolism in women with a recent GDM pregnancy has not been ascertained. We examined the relationships among prolactin, future T2D risk, and key clinical and metabolic parameters. We utilized a prospective GDM research cohort (the SWIFT study) and followed T2D onset by performing 2-hour 75-g research oral glucose tolerance test (OGTT) at study baseline (6-9 weeks postpartum) and again annually for 2 years, and also by retrieving clinical diagnoses of T2D from 2 years through 10 years of follow up from electronic medical records. Targeted metabolomics and lipidomics were applied on fasting plasma samples collected at study baseline from 2-hour 75-g research OGTTs in a nested case-control study (100 future incident T2D cases vs 100 no T2D controls). Decreasing prolactin quartiles were associated with increased future T2D risk (adjusted odds ratio 2.48; 95% CI, 0.81-7.58; P = 0.05). In women who maintained normoglycemia during the 10-year follow-up period, higher prolactin at baseline was associated with higher insulin sensitivity (P = 0.038) and HDL-cholesterol (P = 0.01), but lower BMI (P = 0.001) and leptin (P = 0.002). Remarkably, among women who developed future T2D, prolactin was not correlated with a favorable metabolic status (all P > 0.05). Metabolomics and lipidomics showed that lower circulating prolactin strongly correlated with a T2D-high risk lipid profile, with elevated circulating neutral lipids and lower concentrations of specific phospholipids/sphingolipids. In women with recent GDM pregnancy, low circulating prolactin is associated with specific clinical and metabolic parameters and lipid metabolites linked to a high risk of developing T2D.

Delusion of pregnancy : The role of prolactin

IntroductionA delusion of pregnancy is defined as a fixed false belief that one is pregnant in the absence of any evidence to support the pregnant state. Different mechanisms have been advanced to explain this phenomenon.ObjectivesHerein, we present a case of hyperprolactinemia with delusion of pregnancy during the use of Amisulpride.MethodsHerein, we present a case of hyperprolactinemia with delusion of pregnancy during the use of Amisulpride.ResultsThis case concerns a 39-year-old, divorced Tunisian woman with the diagnosis of schizoaffective disorder,She has never been pregnant. She was taking Amisulpride at the dose of 400 mg per day with 100mg of Haldol Decanoate. In June 2021, she was admitted to our department as she expressed the thought that she was pregnant. No other psychotic symptoms were reported. There was no history of alcohol or illicit drug use. The physical examination was normal. The blood pregnancy test was negative. A measure of serum prolactin was performed and revealed a high prolactin level at 700 ng/ml. Amisulpride was discontinued. We then recorded the serum prolactin level at one month and then at three months after we stopped Amisulpride. We found that as her prolactin levels decreased her complaint of pregnancy also diminished. Actually, the patient has a normal level of prolactin and has no pregnancy delusion.ConclusionsClinicians should be aware that delusion of pregnancy in psychotic patients may be caused by side effects of the treatment. Monitoring of serum prolactin levels in patients under Amisulpride may help to improve the management of these patients.DisclosureNo significant relationships.

Prolactin and its significance in the placenta.

Prolactin, a pituitary hormone that was discovered about 80years ago and is primarily known for its functions in mammary gland development and lactation, is now known to participate in numerous functions across different phylogenetic groups. Fundamentally known for its secretion from lactotroph cells in adenohypophysis region of pituitary gland, newer studies have demonstrated a number of extrapituitary sites which secrete prolactin, where it acts in an autocrine, paracrine, and endocrine manner to regulate essential physiological and biochemical processes. These sites include lymphocytes, epithelial cells of lactating mammary glands, breast cancer cells of epithelial origin, and the placenta. The placenta is one of the most important organs secreting prolactin; however, its role in placental biology has not to date been reviewed comprehensively. This review elaborates upon the various facets of prolactin hormone, including prolactin production and its post-translational modifications and signaling. Major emphasis is placed on placental prolactin and its potential roles, ranging from the role of prolactin in angiogenesis, preeclampsia, maternal diabetes, and anti-apoptosis, among others.

T186 Possible role of prolactin in dysfunctional uterine bleeding

T186 Possible role of prolactin in dysfunctional uterine bleeding

The Role of Oxytocin, Prolactin, and Estrogen in Male Sexual Functions

Background: The dysfunction in sexual ability has effects on the quality of life in men. Oxytocin plays a role in sexual and social behaviors. Hyperprolactemic males had erectile dysfunction. Endogenous estrogens in men, are not only important for health integrity but can additionally cause the promotion of many diseases. Objectives: The current review aimed to high light on the role of oxytocin, prolactin, and estrogen in male sexual functions. Oxytocin neurons have been heavily implicated in mediating sexual behavior in both humans and animals. Oxytocin hormone regulates social behaviors such as mating, maternal/paternal care, and bonding. Oxytocin levels rise during mating in females and males in humans and animals and may mediate anxiolytic/calming effects of sexual activity and antidepressant effects.Oxytocin’s role in regulating erection and ejaculation has been studied in mice and rats. Oxytocinergic projections from the paraventricular nucleus to the hippocampus, medulla oblongata, and spinal cord facilitate penile erection. Prolactin (PRL) serves a dual function both as a circulatory hormone and as a cytokine. PRL is known to be involved in the control of male copulatory behavior in humans, mice, rats, and other rodent models. It release during copulation in males and has a positive modulation for various aspects of testicular functions which hinting at the crucial role of prolactin in male reproduction. The lower concentration of prolactin was associated with reduced seminal vesicle volume and ejaculate in the infertile human male. Hypoprolactinemia has been associated with premature ejaculation and erectile dysfunction. Hyperprolactinemia can be caused by tumors, drugs, or idiopathic, leading to alterations in sexual behavior as loss of libido and erectile dysfunction. It is also reported that it can cause endocrine disturbances leading to abnormal levels of testosterone, FSH, and LH. Chronic hyperprolactinaemia suppresses copulatory behaviour in animal models and yields sexual dysfunction and other side effects in men. In men, testosterone acting via its action on androgen receptors may be dependent on the action of aromatase enzyme on of testosterone and converting it to estradiol (E2). Estrogens act through ERα and ERβ at the plasma membrane and in the nucleus to regulate functions of many organs in men. The role of estradiol action on libido is seen at various levels of regulation, starting with direct effects in the brain. Not only does estradiol modulate sexual behavior in the adult male, it also appears to organize the early brain to program sexual behavior. The exact role of estradiol in each area of male sexual function including libido, spermatogenesis, and erectile function is difficult to determine. A complex balance of testosterone, estradiol, aromatase, and estrogen receptors in brain, testes, and penis, confirmed the indispensable and highly regulated hormonal interaction of estrogen in the male. Conclusion: It can be concluded that oxytocin hormone regulates social behaviors such as mating, maternal/paternal care, and bonding. PRL is involved in the control of male copulatory behavior in humans, rats, mice, and other rodent models. Hypoprolactinemia has been associated with reduced seminal vesicle volume, premature ejaculation, and erectile dysfunction. Hyperprolactinemia can be caused by tumors, drugs, or idiopathic, leading to alterations in sexual behavior as loss of libido and erectile dysfunction. Also, hyperprolactemic males had erectile dysfunction. Estradiol modulates sexual behavior in the adult male, and appears to organize the early brain to program sexual behavior.

Associations among the TREM-1 Pathway, Tau Hyperphosphorylation, Prolactin Expression, and Metformin in Diabetes Mice

Introduction: Diabetes mellitus (DM) is a risk factor for Alzheimer’s disease (AD). Increasing evidence indicates that the triggering receptor expressed on myeloid cells (TREM)-1 amplifies chronic inflammation, as well as the roles of prolactin (PRL) and metformin (MET) in tau hyperphosphorylation. However, the associations among TREM-1, tau hyperphosphorylation, PRL expression, and MET in DM remain unclear. Methods: Streptozotocin was used to induce experimental DM in C57BL/6N mice. MET was orally administered at a dose of 400 mg/kg body weight for 6 weeks prior to hippocampal collection in DM mice. Various parameters pertaining to the TREM-1 pathway, tau hyperphosphorylation, PRL, and related factors were analyzed. Results: Quantitative polymerase chain reaction and Western blot analysis demonstrated that the expression levels of TREM-1, DAP12, casp1, interleukin-1β, Cox2, inducible nitric oxide synthase, pituitary transcriptional factor-1 (Pit-1), and PRL were significantly increased in the hippocampus of DM mice; the expression levels of these pro-inflammatory mediators, PRL receptor (PRLR) short or long (PRLR-S and PRLR-L), and PRL regulatory element-binding (Preb) protein in DM mice treated with MET (DM + MET) were significantly decreased compared with those in control (CON) mice. The levels of p-Tau and glycogen synthase kinase-3 in the DM group were significantly higher than those in the CON group and significantly lower than those in the DM + MET group. Conclusion: We confirmed the therapeutic potential of MET for both DM and neurodegeneration. Our findings shed new light on the effects of DM on the pathophysiology of AD via the TREM-1 pathway and PRL expression. Thus, an improved understanding of the TREM-1 pathway in hyperglycemic conditions, as well as PRL, Preb, Pit-1, PRLR-L, and PRLR-S gene expression in the liver, brain, and other sites, may help unravel the pathogenesis of insulin resistance and neurodegeneration.

The brain as a source and a target of prolactin in mammals.

Prolactin is a polypeptide hormone associated with an extensive variety of biological functions. Among the roles of prolactin in vertebrates, some were preserved throughout evolution. This is the case of its function in the brain, where prolactin receptors, are expressed in different structures of the central nervous system. In the brain, prolactin actions are principally associated with reproduction and parental behavior, and involves the modulation of adult neurogenesis, neuroprotection, and neuroplasticity, especially during pregnancy, thereby preparing the brain to parenthood. Prolactin is mainly produced by specialized cells in the anterior pituitary gland. However, during vertebrate evolution many other extrapituitary tissues do also produce prolactin, like the immune system, endothelial cells, reproductive structures and in several regions of the brain. This review summarizes the relevance of prolactin for brain function, the sources of prolactin in the central nervous system, as well as its local production and secretion. A highlight on the impact of prolactin in human neurological diseases is also provided.

The Expression of Prolactin Receptors in Benign Breast Tumors Is Not Associated with Serum Prolactin Level.

The role of prolactin (PRL) and its receptors in the initiation and development of benign breast tumors (BBT) has not been sufficiently studied. An imbalance in the system of hormone homeostasis is crucial in the development of BBT. In particular, an association between elevated prolactin levels and the development of BBT has been reported. Our study showed no significant differences between PRL receptor (PRL-R) expression in BBT tissue under normal and elevated serum PRL levels. There was also no significant correlation between age, PRL-R expression in BBT tissue, intact tissue, and PRL level in the serum. There was a strong significant correlation (p < 0.01; r = 0.92) between PRL-R expression in BBT samples and intact breast tissue, which did not depend on the serum PRL level. There was also no significant difference in the expression of the proliferative marker Ki-67 in BBT tissues from women with normal and elevated levels of serum PRL (p > 0.05). No signs of PRL and its receptors were detected in the BBT cystic fluid women with elevated serum PRL levels. In summary, our prospective study showed that the expression of PRL-R in the tissue of BBT and physiological breast tissue does not depend on the level of serum PRL.

Regulatory effects of prolactin on breeding and migratory behaviours in birds

Prolactin is an adenohypophyseal hormone of vertebrates produced by the neuroendocrine signaling of the hypothalamus. It plays important role in different vertebrate species and referred to as “The Parental Hormone” or “The Hormone of Maternity”. In birds the role of Prolactin is limited as the parental hormone but the behavioral functions like the regulation of season-al reproduction, combating stress of predators, nest building abilities and regulations of migratory cycle are diversified. The classical role of Prolactin in different birds’ species like pigeons and doves is secretion of crop sac “milk” after hatching of eggs and regulation of migration in different type of mi-grants. Reports have suggested that acute and chronic stressors and ener-getic constraints depress prolactin levels disrupting the parental effort in nest building, mate selection, incubation and crop milk production. Although prolactin is diverse in its function but acts through the same receptors throughout the vertebrate series. However, this review establishes that pro-lactin plays an intense role in regulating breeding behaviours and migration in birds along with the interactions of other hormones. Prolactin helps the birds to carry out wide range of behaviour and become evolutionarily suc-cessful.

PROLACTIN AND HYPERPROLACTINAEMIA IN FEMALE REPRODUCTIVE ENDOCRINOLOGY – AN UPDATE

Hyperprolactinaemia is one of the most frequent causes of anovulation, resulting in infertility and hypoestrogenic state with consequences on overall women’s health. Recent investigations on biological actions of prolactin, especially prolactin of extrapituitary origin, expand our knowledge on prolactin role in the human organism and open new questions connected with female reproductive function and treatment of female infertility. This article represents the review of current knowledge on prolactin physiology, etiopathogenesis, clinical features, assessment , differential diagnosis ,and teatment of hyperprolactinaemia in the female patient.

Efficacy of Vitex agnus in lowering prolactin level in mammary tumor induced SD rats

Introduction and Aim: Breast cancer accounts for about 30% of all cancers in women. The present study aims to see the role of prolactin and Vitex agnus fruit extract in breast cancer progression in mammary tumor induced Sprague Dawley (SD) rats.&#x0D; Materials and Methods: Thirty-day old inbred SD female rats of body weight 70-80 grams were taken for this study. The rats were induced with N- Methyl-Nitroso-Urea for mammary tumor development. After the development of palpable and visible tumor the rats were treated with anti-prolactin drug (Cabergoline) and a prolactin lowering herb Vitex agnus Castus (VAC) for two months. After the treatment the rats were sacrificed for antioxidants estimation and histopathological section examination.&#x0D; Results: The rats treated with anti-prolactin drug showed benign tumors with hyperplasia and lactational change proving the presence of prolactin in the tumor tissue, whereas the plant extract showed mammary tumor regression by the presence of foamy macrophages in the histopathological sections. Results also showed treatment with cabergoline increased the GSH level and decreased the MDA level compared to tumor induced group.&#x0D; Conclusion: Prolactin may have a potential role in progression of breast cancer and Vitex agnus extract showed a prolactin lowering effect and facilitated in regression of the tumor.&#x0D;

Role of prolactin in the regulation of ovarian function in pigs

Role of prolactin in the regulation of ovarian function in pigs

Role of Prolactin and ?-hCG in Female Infertility

Role of Prolactin and ?-hCG in Female Infertility

Inhibition of the Activity of Cyclophilin A Impedes Prolactin Receptor-Mediated Signaling, Mammary Tumorigenesis, and Metastases

SummaryProlactin (PRL) and its receptor (PRLr) play important roles in the pathogenesis of breast cancer. Cyclophilin A (CypA) is a cis-trans peptidyl-prolyl isomerase (PPI) that is constitutively associated with the PRLr and facilitates the activation of the tyrosine kinase Jak2. Treatment with the non-immunosuppressive prolyl isomerase inhibitor NIM811 or CypA short hairpin RNA inhibited PRL-stimulated signaling, breast cancer cell growth, and migration. Transcriptomic analysis revealed that NIM811 inhibited two-thirds of the top 50 PRL-induced genes and a reduction in gene pathways associated with cancer cell signaling. In vivo treatment of NIM811 in a TNBC xenograft lessened primary tumor growth and induced central tumor necrosis. Deletion of CypA in the MMTV-PyMT mouse model demonstrated inhibition of tumorigenesis with significant reduction in lung and lymph node metastasis. The regulation of PRLr/Jak2-mediated biology by NIM811 demonstrates that a non-immunosuppressive prolyl isomerase inhibitor can function as a potential breast cancer therapeutic.

Prolactin may serve as a regulator to promote vocal fold wound healing.

Reduced prolactin (PRL) has been shown to delay wound healing with a limited understanding of the underlying mechanisms. Here, we aim to explore the role of PRL in the repair of vocal fold (VF) injury. A microarray was used to detect the expressed levels of PRL in rat VF tissue at 1, 4, and 8 weeks after VF injury compared with normal uninjured rats. Then, a systematic bioinformatics analysis has been conducted to explore the literature-based biology network and signaling pathways involved in the repair of VF injury. The expression of PRL was significantly decreased in all VF injury groups (week 1, 4, and 8) compared with the control group (F stats = 280.34; P=4.88e-14), with no significant difference among the three VF injury groups (F stats = 1.97; P=0.18). Wounding has been shown to interfere with both PRL-promoting and inhibiting pathways that were involved in wound healing, including 11 PRL inhibitors and 6 PRL promoters. Our results reveal decreased PRL expression levels in VF injury, which is not in favor of the wound healing. The pathways identified may help in understanding the role of PRL as a treatment target for VF wound healing.

An Overview on the Role of Prolactin and its Receptors in the Reproductive System of Women with External Genital Endometriosis

Numerous studies on animal models endow prolactin with multiple functions, both physiological (reproduction, lactation, growth, metabolism, transport and electrolyte behaviour) and pathological (immunity and carcinogenesis). Prolactin is an acidophilic cells hormone of the anterior pituitary gland. For the past decade, there have been many discoveries regarding the functions of prolactin and its receptor (PRL-R). Prolactin has its effect by binding to membrane-bound receptor isoforms, known as long-form and short-form receptors. The PRL-R receptor is expressed in various tissues, such as the mammary gland, prostate gland, ovaries, immune system cells, adipocytes, liver, etc. One of the most well-known functions of prolactin is to stimulate the proliferation and differentiation of breast cells necessary for lactation. Animal models have provided information on the biology of prolactin proteins and give convincing evidence that each prolactin isoform has independent biological functions. It is important to remember that excessive secretion of this hormone is associated with such symptoms as hypogonadism and infertility. Today, up to 40% of all female infertility cases are caused by hyperproduction of prolactin. One of the infertility causes is a combination of hyperprolactinemia and external genital endometriosis, which is currently not well studied. It remains relevant to determine the role of prolactin and dopamine in the pathogenesis of infertility in women with external genital endometriosis and the possibility of using dopamine agonists in the treatment of this disease. This review focuses on the role of prolactin and its receptors in the pathogenesis of infertility associated with endometriosis.

Otx2b mutant zebrafish have pituitary, eye and mandible defects that model mammalian disease.

Combined pituitary hormone deficiency (CPHD) is a genetically heterogeneous disorder caused by mutations in over 30 genes. The loss-of-function mutations in many of these genes, including orthodenticle homeobox 2 (OTX2), can present with a broad range of clinical symptoms, which provides a challenge for predicting phenotype from genotype. Another challenge in human genetics is functional evaluation of rare genetic variants that are predicted to be deleterious. Zebrafish are an excellent vertebrate model for evaluating gene function and disease pathogenesis, especially because large numbers of progeny can be obtained, overcoming the challenge of individual variation. To clarify the utility of zebrafish for the analysis of CPHD-related genes, we analyzed the effect of OTX2 loss of function in zebrafish. The otx2b gene is expressed in the developing hypothalamus, and otx2bhu3625/hu3625 fish exhibit multiple defects in the development of head structures and are not viable past 10days post fertilization (dpf). Otx2bhu3625/hu3625 fish have a small hypothalamus and low expression of pituitary growth hormone and prolactin (prl). The gills of otx2bhu3625/hu3625 fish have weak sodium influx, consistent with the role of prolactin in osmoregulation. The otx2bhu3625/hu3625 eyes are microphthalmic with colobomas, which may underlie the inability of the mutant fish to find food. The small pituitary and eyes are associated with reduced cell proliferation and increased apoptosis evident at 3 and 5 dpf, respectively. These observations establish the zebrafish as a useful tool for the analysis of CPHD genes with variable and complex phenotypes.