Cell Biology Commons^™

Serum Dioxins And Polychlorinated Biphenyls Are Associated With Growth Among Russian Boys, Jane Burns, Paige Williams, Oleg Sergeyev, Susan Korrick, Mary Lee, Boris Revich, Larisa Altshul, Julie Del Prato, Olivier Humblet, Donald Patterson, Wayman Turner, Larry Needham, Mikhail Starovoytov, Russ Hauser

Mary M. Lee

OBJECTIVE: We evaluated the associations of serum dioxins and polychlorinated biphenyls (PCBs) with longitudinally assessed growth measurements among peripubertal Russian boys.

METHODS: A total of 499 boys from Chapaevsk, Russia, aged 8 to 9 years were enrolled in the study from 2003 to 2005 and were followed prospectively for 3 years. Blood samples were collected and physical examinations were conducted at entry and repeated at annual study visits. Multivariate mixed-effects regression models for repeated measures were used to examine the associations of serum dioxins and PCBs with longitudinal measurements of BMI, height, and height velocity.

RESULTS: Serum dioxin (total 2005 …

Measurement Of Mullerian Inhibiting Substance Facilitates Management Of Boys With Microphallus And Cryptorchidism, Madhusmita Misra, David Maclaughlin, Patricia Donahoe, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) is a gonadal hormone expressed in a sexually dimorphic pattern. In males, serum MIS reflects Sertoli cell function and provides an estimate of seminiferous tubular integrity. We examined the role of MIS determination in the evaluation of boys with microphallus (n = 62) and/or cryptorchidism (n = 156). MIS was normal in 69.2% of boys with isolated microphallus compared with 38.1% of boys with microphallus and coexisting cryptorchidism (P < 0.05). In the cryptorchid group, MIS was normal in 46.8%, low in 24.4%, and absent in 28.8%. Normal values for age were associated with testicular tissue, whereas …

Pubertal And Adult Leydig Cell Function In Mullerian Inhibiting Substance-Deficient Mice, Xiufeng Wu, Ramamani Arumugam, Stephen Baker, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) causes Mullerian duct regression during sexual differentiation and regulates postnatal Leydig cell development. MIS knockout (MIS-KO) mice with targeted deletions of MIS develop Leydig cell hyperplasia, but their circulating androgen concentrations are reportedly unaltered. We compared reproductive hormone profiles, androgen biosynthesis, and the expression of key steroidogenic and metabolic enzymes in MIS-KO and wild-type (WT) mice at puberty (36 d) and sexual maturity (60 d). In pubertal animals, basal testosterone and LH concentrations in plasma were lower in MIS-KO than WT mice, whereas human chorionic gonadotropin-stimulated testosterone concentrations were similar. In adults, basal LH, and both …

P19ink4d And P18ink4c Cyclin-Dependent Kinase Inhibitors In The Male Reproductive Axis, Gregory Buchold, Patricia Magyar, Ramamani Arumugam, Mary Lee, Deborah O'Brien

Mary M. Lee

The loss of the cyclin-dependent kinase inhibitors (CKIs) p18(Ink4c) and p19(Ink4d) leads to male reproductive defects (Franklin et al., 1998. Genes Dev 12: 2899-2911; Zindy et al., 2000. Mol Cell Biol 20: 372-378; Zindy et al., 2001. Mol Cell Biol 21: 3244-3255). In order to assess whether these inhibitors directly or indirectly affect male germ cell differentiation, we examined the expression of p18(Ink4c) and p19(Ink4d) in spermatogenic and supporting cells in the testis and in pituitary gonadotropes. Both p18(Ink4c) and p19(Ink4d) are most abundant in the testis after 18 days of age and are expressed in purified populations of spermatogenic …

Dioxin Exposure And Age Of Pubertal Onset Among Russian Boys, Susan A. Korrick, Mary M. Lee, Paige L. Williams, Oleg Sergeyev, Jane S. Burns, Donald G. Patterson, Wayman E. Turner, Larry L. Needham, Larisa Altshul, Boris Revich, Russ Hauser

Mary M. Lee

Background: Animal data demonstrate associations of dioxin, furan, and PCB exposures with altered male gonadal maturation. It is unclear whether these associations apply to human populations. Objectives: We investigated the association of dioxins, furans, PCBs and corresponding toxic equivalent (TEQ) concentrations with pubertal onset among boys in a dioxin-contaminated region. Methods: Between 2003-2005, 489 boys were enrolled at ages 8-9 years in a longitudinal study in Chapaevsk, Russia. Pubertal onset - stages 2 or higher for genitalia (G2+) or testicular volume (TV) > 3 ml - was assessed annually between ages 8-12 years. Serum levels at enrollment were analyzed by the …

Augmented Growth Hormone (Gh) Secretory Burst Frequency And Amplitude Mediate Enhanced Gh Secretion During A Two-Day Fast In Normal Men, Mark Hartman, Johannes Veldhuis, Michael Johnson, Mary Lee, K. Alberti, Eugene Samojlik, Michael Thorner

Mary M. Lee

Serum GH concentrations are increased in fasted or malnourished human subjects. We investigated the dynamic mechanisms underlying this phenomenon in nine normal men by analyzing serum GH concentrations measured in blood obtained at 5-min intervals over 24 h on a control (fed) day and on the second day of a fast with a multiple-parameter deconvolution method to simultaneously resolve endogenous GH secretory and clearance rates. Two days of fasting induced a 5-fold increase in the 24-h endogenous GH production rate [78 +/- 12 vs. 371 +/- 57 micrograms/Lv (Lv, liter of distribution volume) or 0.24 +/- 0.038 vs. 1.1 +/- …

Developmental Expression Of A Candidate Mullerian Inhibiting Substance Type Ii Receptor, Jose Teixeira, Wei He, Paresh Shah, Nobuyuki Morikawa, Mary Lee, Elizabeth Catlin, Peter Hudson, John Wing, David Maclaughlin, Patricia Donahoe

Mary M. Lee

We have isolated a candidate Mullerian inhibiting substance (MIS) type II receptor complementary DNA from an embryonic rat urogenital ridge library and have studied its binding to MIS, its developmental pattern of expression and tissue distribution. By in situ hybridization with a full-length riboprobe, the receptor is expressed in the mesenchymal cells surrounding the Mullerian duct at embryonic days 14, 15, and 16 and in tubular and follicular structures of the rat fetal gonads. Expression of the messenger RNA was also seen in the granules cells and seminiferous tubules of pubertal gonads. Northern analysis revealed that the MIS type II …

Developmentally Regulated Polyadenylation Of Two Discrete Messenger Ribonucleic Acids For Mullerian Inhibiting Substance, Mary Lee, Richard Cate, Patricia Donahoe, Gerald Waneck

Mary M. Lee

Mullerian inhibiting substance (MIS) is a 140-kilodalton homodimeric glycoprotein that causes regression of the Mullerian ducts in male embryos, and may also have a role in both males and females in the regulation of germ cell maturation. We examined the ontogeny of MIS messenger RNA (mRNA) in rat testes from midgestation through adulthood and found two discrete MIS mRNA species that are developmentally regulated. The larger 2.0-kilobase species is abundant at embryonic day 14, then decreases in late gestation, and is barely detectable after birth. The smaller 1.8-kilobase species is first noted at embryonic day 18 and is the major …

Temporal Trends In Serum Concentrations Of Polychlorinated Dioxins, Furans, And Pcbs Among Adult Women Living In Chapaevsk, Russia: A Longitudinal Study From 2000 To 2009, Olivier Humblet, Oleg Sergeyev, Larisa Altshul, Susan A. Korrick, Paige L. Williams, Claude Emond, Linda S. Birnbaum, Jane S. Burns, Mary M. Lee, Boris Revich, Andrey Shelepchikov, Denis Feshin, Russ Hauser

Mary M. Lee

BACKGROUND: The present study assessed the temporal trend in serum concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls (PCBs) among residents of a Russian town where levels of these chemicals are elevated due to prior industrial activity.

METHODS: Two serum samples were collected from eight adult women (in 2000 and 2009), and analyzed with gas chromatography-high-resolution mass spectrometry.

RESULTS: The average total toxic equivalency (TEQ) decreased by 30% (from 36 to 25 pg/g lipid), and the average sum of PCB congeners decreased by 19% (from 291 to 211 ng/g lipid). Total TEQs decreased for seven of the eight women, and the …

Transient Hyperthyroidism In An Adolescent With Hydatidiform Mole, Madhusmita Misra, Lynne Levitsky, Mary Lee

Mary M. Lee

No abstract provided.

Mullerian Inhibiting Substance In Humans: Normal Levels From Infancy To Adulthood, Mary Lee, Patricia Donahoe, Tomonobu Hasegawa, Bernard Silverman, Gretchen Crist, Sharon Best, Yukihiro Hasegawa, Richard Noto, David Schoenfeld, David Maclaughlin

Mary M. Lee

Mullerian-inhibiting substance (MIS) is a gonadal hormone synthesized by Sertoli cells of the testis and granulosa cells of the ovary. To facilitate the use of MIS for the evaluation of intersex disorders and as a tumor marker in women with MIS-expressing ovarian tumors, we measured MIS in 600 serum samples from males and females. These data show that mean MIS values for males rise rapidly during the first year of life and are highest during late infancy, then gradually decline until puberty. In contrast, MIS values in females are lowest at birth and exhibit a minimal increase throughout the prepubertal …

Serum Concentrations Of Organochlorine Pesticides And Growth Among Russian Boys, Jane Burns, Paige Williams, Oleg Sergeyev, Susan Korrick, Mary Lee, Boris Revich, Larisa Altshul, Julie Del Prato, Olivier Humblet, Donald Patterson, Wayman Turner, Mikhail Starovoytov, Russ Hauser

Mary M. Lee

BACKGROUND: Limited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children's growth. OBJECTIVE: We evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels. METHODS: A cohort of 499 boys enrolled in the Russian Children's Study between 2003 and 2005 at 8-9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and …

Mullerian Inhibiting Substance In The Diagnosis And Management Of Intersex And Gonadal Abnormalities, Michael Gustafson, Mary Lee, Lara Asmundson, David Maclaughlin, Patricia Donahoe

Mary M. Lee

Mullerian inhibiting substance (MIS), a gonadal hormone important in sexual differentiation, is high (10 to 70 ng/mL) in human male serum postnatally for several years before declining during the peripubertal period, but is undetectable in female serum until the onset of puberty. The sexually dimorphic secretion of MIS suggested possibilities for its use in several clinical settings. Thirty-one patients with intersex and gonadal anomalies from 17 institutions were therefore evaluated between 1989 and 1992 with an MIS enzyme-linked immunosorbent assay (ELISA). Serum MIS levels correlated with the presence of testicular tissue in two patients with suspected anorchia, five patients with …

Campylobacter Meningitis In Childhood, Mary Lee, Robert Welliver, Leonard La Scolea

Mary M. Lee

No abstract provided.

Predictors Of Serum Dioxin, Furan, And Pcb Concentrations Among Women From Chapaevsk, Russia, Olivier Humblet, Paige Williams, Susan Korrick, Oleg Sergeyev, Claude Emond, Linda Birnbaum, Jane Burns, Larisa Altshul, Donald Patterson, Wayman Turner, Mary Lee, Boris Revich, Russ Hauser

Mary M. Lee

Dioxins, furans, and polychlorinated biphenyls (PCBs) are persistent and bioaccumulative toxic chemicals that are ubiquitous in the environment. We assessed predictors of their serum concentrations among women living in a Russian town contaminated by past industrial activity. Blood samples from 446 mothers aged 23-52 years were collected between 2003-2005 as part of the Russian Children's Study. Serum dioxin, furan, and PCB concentrations were quantified using high-resolution gas chromatography-mass spectrometry. Potential determinants of exposure were collected through interviews. Multivariate linear regression models were used to identify predictors of serum concentrations and toxic equivalencies (TEQs). The median total PCB concentrations and total …

Mentoring Fathers Of Children Newly Diagnosed With T1dm, Susan Sullivan-Bolyai, Carol Bova, Mary Lee, Philip Gruppuso

Mary M. Lee

PURPOSE: To pilot test a social support intervention for fathers of children (T1DM).

DESIGN AND METHODS: The pilot study was part of a larger randomized, controlled clinical trial. Father participants (28 fathers of children newly diagnosed) were recruited from two pediatric diabetes centers. For 12 months fathers (n = 19) and their spouses in the experimental arm received social support (home visits and phone calls). Control group fathers (n = 9) and their spouses received the phone number of an experienced parent (but not formally educated to provide social support) to call as needed.

RESULTS: Fathers in the intervention group …

Key Factors In The Regulation Of Fetal And Postnatal Leydig Cell Development, Xiufeng Wu, Shengqin Wan, Mary Lee

Mary M. Lee

The primary function of testicular Leydig cells is the production of androgens to promote sexual differentiation in the fetus, secondary sexual maturation at puberty, and spermatogenesis in the adult. The fetal and postnatal (adult) populations of Leydig cells differ morphologically and have distinct profiles of gene expression. As postnatal Leydig cells differentiate, they transition through three discrete maturational stages characterized by decreasing proliferative rate and increasing testosterone biosynthetic capacity. In this review, we discuss the development of both fetal and postnatal Leydig cells and review the regulation of this process by some of the key hormones and growth factors.

Consensus Statement On The Use Of Gonadotropin-Releasing Hormone Analogs In Children, Jean-Claude Carel, Erica Eugster, Alan Rogol, Lucia Ghizzoni, Mark Palmert, Mary Lee

Mary M. Lee

OBJECTIVE: Gonadotropin-releasing hormone analogs revolutionized the treatment of central precocious puberty. However, questions remain regarding their optimal use in central precocious puberty and other conditions. The Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology convened a consensus conference to review the clinical use of gonadotropin-releasing hormone analogs in children and adolescents. PARTICIPANTS: When selecting the 30 participants, consideration was given to equal representation from North America (United States and Canada) and Europe, an equal male/female ratio, and a balanced spectrum of professional seniority and expertise. EVIDENCE: Preference was given to articles written in English with long-term …

The Role Of Mullerian Inhibiting Substance In The Evaluation Of Phenotypic Female Patients With Mild Degrees Of Virilization, Madhusmita Misra, David Maclaughlin, Patricia Donahoe, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) is a sexually dimorphic gonadal hormone with proven efficacy in the evaluation of boys with cryptorchidism and children with intersex conditions. We examined the role of MIS determination in the evaluation of 65 phenotypic females with mild virilization. Among the 28 subjects with MIS values elevated above the normal female range, all had abnormal gonadal tissue: ovotestes in 11, testes in 7, dysgenetic gonads in 7, and MIS-secreting ovarian tumors in 3. Among the 37 children with serum MIS in the normal female range, 19 had detectable MIS and 18 had unmeasurable MIS. In the former …

The Influence Of Endocrine Disruptors On Pubertal Timing, Elka Jacobson-Dickman, Mary Lee

Mary M. Lee

PURPOSE OF REVIEW: Overview of the effects of endocrine disruptors on pubertal timing. RECENT FINDINGS: Epidemiologic studies in humans support animal data demonstrating that exposures to endocrine-disrupting compounds have pronounced effects on pubertal timing and that the timing of endocrine-disrupting compound exposure and the specific agent causes different outcomes. Recent studies confirm subtle effects of lead, dioxins, and phytoestrogens on delaying onset of puberty and demonstrate an association of phthalates and polychlorinated biphenyls with earlier breast development and menarche, respectively. These studies, however, are complicated by mixed exposures of compounds which individually may have opposing actions on the reproductive axis. …

Pseudohypoparathyroidism Type 1a And Insulin Resistance In A Child, Benjamin U. Nwosu, Mary M. Lee

Mary M. Lee

Background. A 5-year-old white girl with a history of hypothyroidism in infancy presented to the endocrinology clinic of a tertiary hospital. Her physical examination noted a stocky physique, broad chest, short neck and short digits. Two years later, skin examination revealed subcutaneous nodules and acanthosis nigricans. Investigations. Measurement of levels of serum phosphate, parathyroid hormone, ionized calcium and insulin; measurement of peak growth hormone by the arginine-levodopa stimulation test; calculation of homeostasis model assessment of insulin resistance; assessment of bone age; DNA analysis of the GNAS gene. Diagnosis. Pseudohypoparathyroidism type 1a in a patient with Albright hereditary osteodystrophy, characterized by …

Alterations In The Pulsatile Mode Of Growth Hormone Release In Men And Women With Insulin-Dependent Diabetes Mellitus, Christopher Asplin, Amilton Faria, Elizabeth Carlsen, Veronica Vaccaro, Richard Barr, Ali Iranmanesh, Mary Lee, Johannes Veldhuis, William Evans

Mary M. Lee

The mechanisms responsible for the elevated levels of circulating GH observed in diabetes mellitus (DM) remain incompletely defined. To assess the episodic fluctuations in serum GH as a reflection of hypothalamic-pituitary activity, we accumulated GH concentration-time series in a total of 48 adult men and women with and without insulin-dependent DM by obtaining serum samples at 10-min intervals over 24 h. Significant pulses of GH release were subsequently identified and characterized by an objective, statistically based pulse detection algorithm (Cluster) and fixed circadian (24-h) periodicities of secretory activity, resolved using Fourier expansion timeseries analysis. Compared to those in age-matched controls, …

Predictors Of Serum Dioxins And Pcbs Among Peripubertal Russian Boys, Jane S. Burns, Paige L. Williams, Oleg Sergeyev, Susan Korrick, Mary M. Lee, Boris Revich, Larisa Altshul, Donald G. Patterson, Wayman E. Turner, Larry L. Needham, Igor Saharov, Russ Hauser

Mary M. Lee

BACKGROUND: Although sources and routes of exposure to dioxins and polychlorinated biphenyls (PCBs) have been studied, information regarding exposure among children is limited. Breast-feeding and diet are two important contributors to early life exposure. To further understand other significant contributors to childhood exposure, we studied a cohort of children from a city with high environmental dioxin levels. OBJECTIVES: We investigated predictors of serum concentrations of polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzofurans (PCDFs)/co-planar PCBs (C-PCBs), toxic equivalents (TEQs), and PCBs among 8- to 9-year-old boys in Chapaevsk, Russia. METHODS: We used general linear regression models to explore associations of log(10)-transformed serum concentrations of …

Hypothyroidism In Down Syndrome: Screening Guidelines And Testing Methodology, Olga Hardy, Gordon Worley, Mary Lee, Shu Chaing, Joanne Mackey, Blythe Crissman, Priya Kishnani

Mary M. Lee

No abstract provided.

Mullerian Inhibiting Substance As A Marker For Ovarian Sex-Cord Tumor, Michael Gustafson, Mary Lee, Robert Scully, Ashby Moncure, Toshio Hirakawa, Annekathryn Goodman, Howard Muntz, Patricia Donahoe, David Maclaughlin, Arlan Fuller

Mary M. Lee

No abstract provided.

Mullerian-Inhibiting Substance Inhibits Rat Leydig Cell Regeneration After Ethylene Dimethanesulphonate Ablation, Antonio Salva, Matthew Hardy, Xiufeng Wu, Chantal Sottas, David Maclaughlin, Patricia Donahoe, Mary Lee

Mary M. Lee

The postnatal development of Leydig cell precursors is postulated to be controlled by Sertoli cell secreted factors, which may have a determinative influence on Leydig cell number and function in sexually mature animals. One such hormone, Mullerian inhibiting substance (MIS), has been shown to inhibit DNA synthesis and steroidogenesis in primary Leydig cells and Leydig cell tumor lines. To further delineate the effects of MIS on Leydig cell proliferation and steroidogenesis, we employed the established ethylene dimethanesulphonate (EDS) model of Leydig cell regeneration. Following EDS ablation of differentiated Leydig cells in young adult rats, recombinant MIS or vehicle was delivered …

Mullerian Inhibiting Substance Recruits Alk3 To Regulate Leydig Cell Differentiation, Xiufeng Wu, Ningning Zhang, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) not only induces Mullerian duct regression during male sexual differentiation but also modulates Leydig cell steroidogenic capacity and differentiation. MIS actions are mediated through a complex of homologous receptors: a type II ligand-binding receptor [MIS type II receptor (MISRII)] and a tissue-specific type I receptor that initiates downstream signaling. The putative MIS type I receptors responsible for Mullerian duct regression are activin A type II receptor, type I [Acvr1/activin receptor-like kinase 2 (ALK2)], ALK3, and ALK6, but the one recruited by MIS in Leydig cells is unknown. To identify whether ALK3 is the specific type I …

Association Of Blood Lead Levels With Onset Of Puberty In Russian Boys, Russ Hauser, Oleg Sergeyev, Susan Korrick, Mary M. Lee, Boris Revich, Elana Gitin, Jane S. Burns, Paige L. Williams

Mary M. Lee

BACKGROUND: Epidemiologic studies suggest a temporal trend of earlier onset and longer duration of puberty, raising concerns regarding the potential impact of environmental factors on pubertal development. Lead exposure has been associated with delayed pubertal onset in girls; however, epidemiologic data in boys are limited. METHODS: We used multivariable logistic regression models to explore the cross-sectional association of blood lead levels with growth and pubertal onset based on physician-assessed testicular volume (TV) and pubertal staging in 489 boys 8-9 years of age from Chapaevsk, Russia. We used multivariable linear regression models to assess associations of blood lead levels with somatic …

Mullerian Inhibiting Substance Is Present In Embryonic Testes Of Dogs With Persistent Mullerian Duct Syndrome, Vicki Meyers-Wallen, Mary Lee, T. Manganaro, T. Kuroda, David Maclaughlin, Patricia Donahoe

Mary M. Lee

Mullerian Inhibiting Substance (MIS) causes regression of the Mullerian ducts during a critical period in embryonic development in male mammals. In Persistent Mullerian Duct Syndrome (PMDS), an autosomal recessive trait in humans and dogs, the Mullerian ducts fail to regress in otherwise normal males. Previously we reported that PMDS-affected dogs produce bioactive testicular MIS postnatally. The purpose of the present study was to determine whether PMDS-affected canine embryos appropriately express MIS mRNA and protein during the critical period for Mullerian duct regression. Homozygous (PMDS-affected) and normal canine embryos were removed from timed pregnancies. Gonadal sex and the degree of Mullerian …

Mis/Amh In The Assessment Of Cryptorchidism And Intersex Conditions, Mary Lee, Madhusmita Misra, Patricia Donahoe, David Maclaughlin

Mary M. Lee

Mullerian inhibiting substance (MIS), also known as anti-Mullerian hormone (AMH), causes Mullerian duct involution during male sexual differentiation and also has a postnatal regulatory role in the gonads. Serum MIS/AMH has a gonad specific pattern of expression and its concentrations are sexually dimorphic in children; hence measurement of serum MIS/AMH helps in the evaluation of children with gonadal disorders. In boys with cryptorchidism (non-palpable gonads), serum MIS/AMH correlates with testicular tissue. A measurable value is predictive of undescended testes while an undetectable value is highly suggestive of anorchia. In minimally virilized phenotypic females, MIS/AMH helps differentiate between gonadal and non-gonadal …