Top Surgery and Chest Dysphoria Among Transmasculine and Nonbinary Adolescents and Young Adults.

Importance: Transgender and nonbinary (TGNB) adolescents and young adults (AYA) designated female at birth (DFAB) experience chest dysphoria, which is associated with depression and anxiety. Top surgery may be performed to treat chest dysphoria. Objective: To determine whether top surgery improves chest dysphoria, gender congruence, and body image in TGNB DFAB AYA. Design, Setting, and Participants: This is a nonrandomized prospective cohort study of patients who underwent top surgery between December 2019 and April 2021 and a matched control group who did not receive surgery. Patients completed outcomes measures preoperatively and 3 months postoperatively. This study took place across 3 institutions in a single, large metropolitan city. Patients aged 13 to 24 years who presented for gender-affirming top surgery were recruited into the treatment arm. Patients in the treatment arm were matched with individuals in the control arm based on age and duration of testosterone therapy. Exposures: Patients in the surgical cohort underwent gender-affirming mastectomy; surgical technique was at the discretion of the surgeon. Main Outcomes and Measures: Patient-reported outcomes were collected at enrollment and 3 months postoperatively or 3 months postbaseline for the control cohort. The primary outcome was the Chest Dysphoria Measure (CDM). Secondary outcomes included the Transgender Congruence Scale (TCS) and Body Image Scale (BIS). Baseline demographic and surgical variables were collected, and descriptive statistics were calculated. Inverse probability of treatment weighting (IPTW) was used to estimate the association of top surgery with outcomes. Probability of treatment was estimated using gradient-boosted machines with the following covariates: baseline outcome score, age, gender identity, race, ethnicity, insurance type, body mass index, testosterone use duration, chest binding, and parental support. Results: Overall, 81 patients were enrolled (mean [SD] age, 18.6 [2.7] years); 11 were lost to follow-up. Thirty-six surgical patients and 34 matched control patients completed the outcomes measures. Weighted absolute standardized mean differences were acceptable between groups with respect to body mass index, but were not comparable with respect to the remaining demographic variables baseline outcome measures. Surgical complications were minimal. IPTW analyses suggest an association between surgery and substantial improvements in CDM (-25.58 points; 95% CI, -29.18 to -21.98), TCS (7.78 points; 95% CI, 6.06-9.50), and BIS (-7.20 points; 95% CI, -11.68 to -2.72) scores. Conclusions and Relevance: Top surgery in TGNB DFAB AYA is associated with low complication rates. Top surgery is associated with improved chest dysphoria, gender congruence, and body image satisfaction in this age group.

Supporting the Health of Transgender and Gender-Diverse Youth in Primary Care Settings.

Transgender and gender-diverse youth represent approximately 2% of all youth in the United States. Given that gender diversity usually develops during childhood and adolescence, primary care providers must be equipped to recognize and support youth exploring gender identity or experiencing gender dysphoria. This article provides an overview of gender diversity and reviews strategies for creating a welcoming clinical space, discussing gender during the office visit, providing affirming primary care, and supporting youth and their families during gender identity exploration and gender transition.

Association of Chest Dysphoria With Anxiety and Depression in Transmasculine and Nonbinary Adolescents Seeking Gender-Affirming Care.

PURPOSE: The purpose of this study was to determine the existence and strength of association between chest dysphoria and mental health in transmasculine and nonbinary adolescents. METHODS: This is a cross-sectional cohort study of transmasculine and nonbinary adolescents designated female at birth between 12 and 18 years old. None had undergone prior top surgery. Patients complete the Chest Dysphoria Measure and Youth Inventory-4 (YI-4) upon presentation to our institution. Outcomes were retrospectively reviewed. The primary outcome of interest was the association between chest dysphoria and anxiety and depression symptom severity, as measured by the YI-4. RESULTS: One hundred fifty-six patients met inclusion criteria. Mean age was 15.3 years (standard deviation [SD] = 1.7). Most patients identified as transmasculine (n = 132); 18 identified as nonbinary and 6 as questioning. Mean (SD) YI-4 symptom severity scores were 10.67 (6.64) for anxiety and 11.99 (7.83) for depression. Mean (SD) Chest Dysphoria Measure composite score was 30.15 (9.95); range 2-49. Chest dysphoria was positively correlated with anxiety (r = .146; p = .002) and depression (r = .207; p < .001). In multivariate linear regression models, chest dysphoria showed a significant, positive association with anxiety and depression, after accounting for gender dysphoria, degree of appearance congruence, and social transition status. CONCLUSIONS: Chest dysphoria is associated with higher anxiety and depression in transmasculine and nonbinary adolescents designated female at birth. This association is independent of level of gender dysphoria, degree of appearance congruence, and social transition status. Treatment options aimed at alleviating chest dysphoria should be made accessible to adolescents and tailored to individual needs.

Effect of Concurrent Gonadotropin-Releasing Hormone Agonist Treatment on Dose and Side Effects of Gender-Affirming Hormone Therapy in Adolescent Transgender Patients.

This retrospective chart review aims to address gaps in the literature regarding the efficacy and interaction of gonadotropin-releasing hormone agonists (GnRHa) and gender-affirming hormone therapies in medical transition regimens in transgender adolescents. We abstracted and reviewed data from 83 patients at our pediatric gender clinic, and found that patients who initiated treatment with GnRHa before gender-affirming hormones (estrogen, testosterone) required lower doses of those hormones than those who did not use GnRHa. The results of this preliminary research provide a foundation for future long-term prospective studies aimed to better understand these relationships.

Ethical Considerations in Fertility Preservation for Transgender Youth: A Case Illustration.

Increasing numbers of transgender adolescents are presenting for transition-related medical care, including gender-affirming estrogen and testosterone. The decision to transition with hormones has long-term implications, including possible irreversible impairment of future reproductive functioning. The commentary by Hudson, Nahata, Dietz, and Quinn (2017) outlines the importance of fertility counseling for transgender adolescents and young adults as ethical, interdisciplinary practice. Key considerations raised include implementing shared decision-making strategies that account for youths' maturity and individual decisional capacity, evaluating co-occurring psychiatric conditions that could interfere with future-oriented decision-making, and considering benefits and harms of fertility preservation (FP) in the context of a youth's values, identity, and comfort. This report includes two case illustrations of transmasculine youth which highlight how ethical considerations emerge in clinical practice and underscore the nuance and complexity of fertility-related decision-making among transgender adolescents.

Fertility Preservation for Transgender Adolescents.

PURPOSE: To describe fertility preservation (FP) utilization by transgender adolescents within a pediatric gender clinic between July 2013 and July 2016. METHODS: A retrospective chart review was conducted to abstract demographic and clinical information among adolescents initiating gender-affirming hormones, including patient age at initial FP consultation, birth-assigned sex, race/ethnicity, and outcome of FP consultation. RESULTS: In our sample of 105 transgender adolescents, a total of 13 (seven transgender men and six transgender women) between the age of 14.2 and 20.6 years were seen in formal consultation for FP before initiating hormones. Of these adolescents, four completed sperm cryopreservation and one completed oocyte cryopreservation. CONCLUSIONS: Rates of FP utilization among transgender youth were low, which is consistent with a recently published report of FP utilization among transgender youth at another pediatric institution. Identified barriers to FP in our sample included cost, invasiveness of procedures, and desire not to delay medical transition.

Epigenetic regulation of hematopoiesis by DNA methylation.

During embryonic development, cell type-specific transcription factors promote cell identities, while epigenetic modifications are thought to contribute to maintain these cell fates. Our understanding of how genetic and epigenetic modes of regulation work together to establish and maintain cellular identity is still limited, however. Here, we show that DNA methyltransferase 3bb.1 (dnmt3bb.1) is essential for maintenance of hematopoietic stem and progenitor cell (HSPC) fate as part of an early Notch-runx1-cmyb HSPC specification pathway in the zebrafish. Dnmt3bb.1 is expressed in HSPC downstream from Notch1 and runx1, and loss of Dnmt3bb.1 activity leads to reduced cmyb locus methylation, reduced cmyb expression, and gradual reduction in HSPCs. Ectopic overexpression of dnmt3bb.1 in non-hematopoietic cells is sufficient to methylate the cmyb locus, promote cmyb expression, and promote hematopoietic development. Our results reveal an epigenetic mechanism supporting the maintenance of hematopoietic cell fate via DNA methylation-mediated perdurance of a key transcription factor in HSPCs.

Proceedings of the Working Group Session on Fertility Preservation for Individuals with Gender and Sex Diversity.

Children and adolescents with gender and sex diversity include (1) gender-nonconforming and transgender individuals for whom gender identity or expression are incongruent with birth-assigned sex (heretofore, transgender) and (2) individuals who have differences in sex development (DSD). Although these are largely disparate groups, there is overlap in the medical expertise necessary to care for individuals with both gender and sex diversity. In addition, both groups face potential infertility or sterility as a result of desired medical and surgical therapies. The Ann & Robert H. Lurie Children's Hospital of Chicago (Lurie Children's) gender and sex development program (GSDP) provides specialized multidisciplinary care for both transgender and DSD patients. In response to patient concerns that recommended medical treatments have the potential to affect fertility, the Lurie Children's GSDP team partnered with experts from the Oncofertility Consortium at Northwestern University to expand fertility preservation options to gender and sex diverse youth. This article summarizes the results of a meeting of experts across this field at the annual Oncofertility Consortium conference with thoughts on next steps toward a unified protocol for this patient group.

Multidisciplinary Care for Gender-Diverse Youth: A Narrative Review and Unique Model of Gender-Affirming Care.

Heightened public awareness about gender diversity in childhood and adolescence has resulted in more youth and families seeking medical and mental health services. In response to these needs, there has been nationwide growth in specialized multidisciplinary clinics treating gender-diverse and transgender youth. Despite general agreement that comprehensive treatment is best delivered through a multidisciplinary team by both medical and mental health clinicians with gender-related expertise and familiarity with child and adolescent development, there is currently no consensus regarding the best approach to clinical care with gender-diverse and transgender youth. In this article, we provide a narrative review of the gender affirmative model guiding our clinical practice and describe the development of our unique model of affirming care within the Gender and Sex Development Program at the Ann & Robert H. Lurie Children's Hospital of Chicago.

Baseline Physiologic and Psychosocial Characteristics of Transgender Youth Seeking Care for Gender Dysphoria.

PURPOSE: The purpose of this study was to describe baseline characteristics of participants in a prospective observational study of transgender youth (aged 12-24 years) seeking care for gender dysphoria at a large, urban transgender youth clinic. METHODS: Eligible participants presented consecutively for care at between February 2011 and June 2013 and completed a computer-assisted survey at their initial study visit. Physiologic data were abstracted from medical charts. Data were analyzed by descriptive statistics, with limited comparisons between transmasculine and transfeminine participants. RESULTS: A total of 101 youth were evaluated for physiologic parameters, 96 completed surveys assessing psychosocial parameters. About half (50.5%) of the youth were assigned a male sex at birth. Baseline physiologic values were within normal ranges for assigned sex at birth. Youth recognized gender incongruence at a mean age of 8.3 years (standard deviation = 4.5), yet disclosed to their family much later (mean = 17.1; standard deviation = 4.2). Gender dysphoria was high among all participants. Thirty-five percent of the participants reported depression symptoms in the clinical range. More than half of the youth reported having thought about suicide at least once in their lifetime, and nearly a third had made at least one attempt. CONCLUSIONS: Baseline physiologic parameters were within normal ranges for assigned sex at birth. Transgender youth are aware of the incongruence between their internal gender identity and their assigned sex at early ages. Prevalence of depression and suicidality demonstrates that youth may benefit from timely and appropriate intervention. Evaluation of these youth over time will help determine the impact of medical intervention and mental health therapy.

Understanding gender variance in children and adolescents.

Gender variance is an umbrella term used to describe gender identity, expression, or behavior that falls outside of culturally defined norms associated with a specific gender. In recent years, growing media coverage has heightened public awareness about gender variance in childhood and adolescence, and an increasing number of referrals to clinics specializing in care for gender-variant youth have been reported in the United States. Gender-variant expression, behavior, and identity may present in childhood and adolescence in a number of ways, and youth with gender variance have unique health needs. For those experiencing gender dysphoria, or distress encountered by the discordance between biological sex and gender identity, puberty is often an exceptionally challenging time. Pediatric primary care providers may be families' first resource for education and support, and they play a critical role in supporting the health of youth with gender variance by screening for psychosocial problems and health risks, referring for gender-specific mental health and medical care, and providing ongoing advocacy and support.

Parental support and mental health among transgender adolescents.

PURPOSE: Family support is protective against health risks in sexual minority individuals. However, few studies have focused specifically on transgender youth, who often experience rejection, marginalization, and victimization that place them at risk for poor mental health. This study investigated the relationships among parental support, quality of life, and depression in transgender adolescents. METHODS: A total of 66 transgender youth presenting for care at Children's Hospital Los Angeles completed a survey assessing parental support (defined as help, advice, and confidante support), quality of life, and depression. Regression analyses assessed the associations between parental support and mental health outcomes. RESULTS: Parental support was significantly associated with higher life satisfaction, lower perceived burden of being transgender, and fewer depressive symptoms. CONCLUSIONS: Parental support is associated with higher quality of life and is protective against depression in transgender adolescents. Interventions that promote parental support may significantly affect the mental health of transgender youth.

Phase II study of biweekly pemetrexed and gemcitabine in patients with previously untreated advanced non-small cell lung cancer.

INTRODUCTION: Pemetrexed and gemcitabine are safe and active non-small cell lung cancer (NSCLC) therapies when administered every 3 weeks. Biweekly scheduling was studied in this phase II trial. METHODS: The primary objective was to assess the overall response rate in chemotherapy-naive patients with unresectable stage III/IV NSCLC. Patients received 500 mg/m(2) of pemetrexed intravenously and 1500 mg/m(2) of gemcitabine intravenously every 2 weeks for 8 to 12 cycles with restaging every 4 cycles. Patients also received supplemental folate/B12 therapy. Entry criteria included the following: all non-small cell histologies, measurable disease, Eastern Cooperative Oncology Group 0 to 2, and informed consent. RESULTS: Seventy-two patients were enrolled. Baseline characteristics included the following: median age: 66 years (41-85 years); male/female: 65%/35%; Eastern Cooperative Oncology Group 0/1/2: 19%/67%/14%; and histology: adenocarcinoma (36%), large cell (18%), squamous (13%), and mixed or not specified (34%). The median number of cycles was 7 (range, 1-12). The most common (> or =5%) grade 3/4 toxicities were as follows: neutropenia (47%), leukopenia (31%), fatigue (25%), dyspnea (18%), pain (11%), and anemia (8%). Complete/partial responses for all patients: 1 patient/18 patients, respectively, for an overall response rate of 26% (95% confidence interval, 17-38%). Thirty-nine percentage of patients had stable disease, and 21% had disease progression (10 patients were not evaluable). Median progression-free survival was 6.2 months. One-year overall survival was 37.5%. CONCLUSION: Biweekly administration of pemetrexed and gemcitabine seems to be well tolerated with activity comparable with other first-line NSCLC regimens. Further study addressing whether biweekly scheduling could be an effective strategy to shorten overall treatment duration will require a randomized design.

A phase II trial of gemcitabine/carboplatin with or without trastuzumab in the first-line treatment of patients with metastatic breast cancer.

PURPOSE: The purpose of this study was to evaluate the efficacy and toxicity of the combination of gemcitabine and carboplatin (and with trastuzumab in patients with HER2-positive disease) as first-line treatment for patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Seventy-four patients who had received no previous chemotherapy for MBC were enrolled. Patients with HER2-negative breast cancer received treatment with gemcitabine 1000 mg/m(2) intravenously (I.V.) on days 1 and 8 and carboplatin area under the curve (AUC) 5 I.V. on day 1. Cycles were repeated every 21 days. Patients with HER2-positive disease also received trastuzumab 8-mg/kg I.V. loading dose, then 6 mg/kg I.V. every 21 days. After the first 29 patients were treated, the carboplatin dose was lowered to AUC 4. Patients were re-evaluated every 6 weeks; responses were measured using Response Evaluation Criteria in Solid Tumors criteria. RESULTS: In patients with HER2-negative disease, gemcitabine/carboplatin produced a 34% major response rate; an additional 28% of patients had stable disease > or = 6 months (overall disease control rate, 62%). Gemcitabine/carboplatin/trastuzumab produced an overall response rate of 66%, with a disease control rate of 77%. Grade 3/4 myelosuppression was common, even after reduction of the carboplatin dose. Only 3 patients treated with the lower dose regimen developed neutropenia and fever, but platelet and red blood cell transfusions were necessary in 24% and 40% of patients, respectively. Trastuzumab did not add to hematologic toxicity. Severe nonhematologic toxicity was uncommon. CONCLUSION: Gemcitabine/carboplatin and gemcitabine/carboplatin/trastuzumab are active first-line regimens for patients with MBC. The gemcitabine/carboplatin combination causes more grade 3/4 myelosuppression than other standard combination regimens for MBC; however, severe nonhematologic toxicity is minimal.

Development of a pituitary-specific cre line targeted to the Pit-1 lineage.

Tissue-specific expression of the Cre recombinase is a well-established genetic tool to analyze gene function in specific tissues and cell types. In this report, we describe the generation of a new transgenic line that expresses Cre under the control of the rat growth hormone releasing hormone receptor (rGhrhr) promoter. This promoter, chosen to target the anterior pituitary, drives cre-mediated recombination in cells of the Pit1 lineage, including somatotrophs, lactotrophs, and thyrotrophs. Cre activity is first detected at embryonic day 13.5, and gradually increases to reach high level expression by postnatal day 2. In addition to the pituitary, rGhrhr-cre expression was detected in vibrissae and in hair follicles of the proximal limb, but not in other tissues. The rGhrhr-cre line will be a valuable tool for the study of the development of the pituitary Pit1 lineage and for the study of tumorigenesis involving these cells.

Pituitary-specific knockout of the Carney complex gene Prkar1a leads to pituitary tumorigenesis.

Carney complex (CNC) is an inherited neoplasia syndrome characterized by spotty skin pigmentation, myxomas, endocrine tumors, and schwannomas. Among the endocrine tumors that comprise the syndrome, GH-producing pituitary tumors are seen in approximately 10% of patients, although biochemical abnormalities of the GH axis are much more common. To explore the role of loss of the CNC gene PRKAR1A on pituitary tumorigenesis, we produced a tissue-specific knockout (KO) of this gene in the mouse. For these studies, we generated a mouse line expressing the cre recombinase in pituitary cells using the rat GHRH receptor promoter. These mice were then crossed with Prkar1a conditional null animals to produce tissue-specific KOs. Although prolactinomas were observed in KO and control mice, the KO mice exhibited a significantly increased frequency of pituitary tumors compared with wild-type or conventional Prkar1a(+/-) mice. Characterization of the tumors demonstrated they were composed of cells of the Pit1 lineage that stained for GH, prolactin, and TSH. At the biochemical level, levels of GH in the serum of KO animals were markedly elevated compared with controls, regardless of the presence of a frank tumor. These data indicate that complete loss of Prkar1a is sufficient to allow the formation of pituitary tumors and abnormalities of the GH axis, in close analogy to human patients with CNC.

Irinotecan, carboplatin, and imatinib in untreated extensive-stage small-cell lung cancer: a phase II trial of the Minnie Pearl Cancer Research Network.

INTRODUCTION: The tyrosine kinase KIT has variable expression in small-cell lung cancer (SCLC) and may be a prognostic factor. Imatinib targets KIT expression, providing rationale for studying its role in combination with chemotherapy in SCLC in a multicenter phase II trial. METHODS: Patients with untreated extensive-stage SCLC received carboplatin area under the concentration-time curve of 4 on day 1; irinotecan 60 mg/m2 on days 1, 8, and 15; and imatinib 600 mg/day. Treatment cycles were 28 days. Patients remained on imatinib until progressive disease or significant toxicity. RESULTS: Between September 2002 and May 2004, 68 patients were enrolled in this multicenter trial. Median age was 60 years (range, 37-81). The objective response rate was 66% (95% confidence interval: 54%-76%). Median progression-free survival was 5.4 months (95% CI: 4.3-6.0 months). Median overall survival was 8.4 months (95% CI: 6.3-10.5 months). Thirty-five percent of patients were alive at 1 year. Grade 3/4 hematologic toxicity included neutropenia (43%), anemia (16%), and thrombocytopenia (9%). Grade 3 nonhematologic toxicity included diarrhea (19%), fatigue (24%), and nausea (26%). Forty-eight of 56 patients (86%) with available tumor specimens had KIT expression detected. KIT expression did not appear to correlate with progression-free survival or overall survival in a retrospective analysis. CONCLUSIONS: Irinotecan, carboplatin, and imatinib is a safe and generally well-tolerated regimen in patients with SCLC. However, the addition of imatinib did not improve results from those expected with chemotherapy alone.

Weekly docetaxel and bortezomib as first-line treatment for patients with hormone-refractory prostate cancer: a Minnie Pearl Cancer Research Network phase II trial.

BACKGROUND: Docetaxel is currently the standard first-line treatment in patients with hormone-refractory prostate cancer (HRPC). Bortezomib, the first proteasome inhibitor in clinical use, demonstrated activity against prostate cancer in phase I trials. For this reason, we evaluated the efficacy of docetaxel plus bortezomib in the first-line treatment of patients with HRPC. PATIENTS AND METHODS: Between February 2004 and May 2005, 63 eligible patients entered this phase II trial. All patients had metastatic adenocarcinoma of the prostate that had progressed on hormonal therapy. All patients received docetaxel 30 mg/m(2) and bortezomib 1.6 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. Patients were reevaluated after 8 weeks of treatment; responding and stable patients continued treatment until tumor progression. RESULTS: Sixty patients (95%) received > or = 2 courses of treatment and were evaluable for response. Fifteen patients (25%; 95% confidence interval, 15%-38%) had a > 50% decrease in serum prostate-specific antigen level with treatment; the median response duration was 8 months. The median progression-free and overall survival times for the entire group were 4.1 months and 13.8 months, respectively; 20% of patients were alive at 2 years. The regimen was well tolerated, with uncommon grade 3/4 toxicity. CONCLUSION: Treatment with this combination of weekly docetaxel and bortezomib showed no suggestion of improved efficacy versus previous results with docetaxel alone. Bortezomib has minimal activity in patients with HRPC and is unlikely to make any impact on treatment efficacy.

Urokinase-type plasminogen activator mRNA is expressed in normal developing teeth and leads to abnormal incisor enamel in alpha MUPA transgenic mice.

The urokinase-type plasminogen activator (uPA) is a secreted, inducible serine protease implicated in extracellular proteolysis and tissue remodeling. Here we detected uPA mRNA through in situ hybridization in developing molar and incisor teeth of normal mice at multiple sites of the cap and bell developmental stages. The mRNA was confined to epithelial cells, however, was undetectable in ameloblasts or their progenitor preameloblasts and the inner enamel epithelium. Furthermore, mice of five lines of previously described alphaMUPA transgenic mice, carrying a transgene consisting of the uPA cDNA linked downstream from the alphaA-crystallin promoter, overexpressed uPA mRNA in the same epithelial sites. In addition, alphaMUPA mice showed remarkably high levels of uPA mRNA in ameloblasts, however, exclusively in two specific sites late in incisor development. First, at the late secretory stage, but only on sides of the ameloblast layer. Second, in a limited zone of ameloblasts near the incisal end, coinciding with a striking morphological change of the ameloblast layer and the enamel matrix. In adult alphaMUPA mice, the incisor teeth displayed discoloration and tip fragility, and reduction of the outer enamel as determined by scanning electron microscopy. These results suggest that balanced uPA activity could play a role in normal tooth development. The alphaMUPA tooth phenotype demonstrates a remarkable sensitivity to excessive extracellular proteolysis at the incisor maturation stage of amelogenesis.

A novel inducible element, activated by contact with Rathke's pouch, is present in the regulatory region of the Rpx/Hesx1 homeobox gene.

Reciprocal inductive interactions are postulated to play a role in the determination and differentiation of the pituitary gland and the ventral hypothalamus. The homeobox gene Rpx/Hesxl is expressed during gastrulation in the anterior endoderm, prechordal plate, and the prospective cephalic neural plate, and at later stages of development in Rathke's pouch, the primordium of the pituitary. We have defined the regulatory elements necessary for proper spatial and temporal expression during development in transgenic mice using lacZ reporter genes. Proper spatial and temporal expression in the anterior endoderm prechordal plate and anterior neural plate can be recapitulated with as little as 568 bp of upstream sequence and intragenic sequence containing the first exon and intron. Late-stage expression in Rathke's pouch requires additional negative and positive regulatory elements. Interestingly, deletion analysis uncovered an element that directs transgene expression to a region of the hypothalamus that lies in direct contact with Rathke's pouch. In vitro tissue recombination experiments have established that this expression is induced by contact with the pouch. We propose that this element may be present in other genes that normally respond to signals emanating from the pouch during the development of the hypothalamic-pituitary axis. The Rpx-lacZ transgenic mice provide a novel model system for the molecular dissection of inductive cell signaling during pituitary development.