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GABA has been proposed to inhibit insulin secretion through [GABA.sub.B] receptors ([GABA.sub.B]Rs) in pancreatic [beta]-cells. We investigated whether [GABA.sub.B]Rs participated in the regulation of glucose homeostasis in vivo. The animals used in this study were adult male and female BALB/C mice, mice deficient in the [GABA.sub.B1] subunit of the [GABA.sub.B]R ([GABA.sub.B.sup.-/-]), and wild types (WT). Blood glucose was measured under fasting/fed conditions and in glucose tolerance tests (GTTs) with a Lifescan Glucose meter, and serum insulin was measured by ELISA. Pancreatic insulin content and islet insulin were released by RIA. Western blots for the [GABA.sub.B1] subunit in islet membranes and immunohistochemistry for insulin and [GABA.sub.B1] were performed in both genotypes. BALB/C mice preinjected with Baclofen ([GABA.sub.B]R agonist, 7.5 mg/kg ip) presented impaired GTTs and decreased insulin secretion compared with saline-preinjected controls. [GABA.sub.B.sup.-/-] mice showed fasting and fed glucose levels similar to WT. [GABA.sub.B.sup.-/-] mice showed improved GTTs at moderate glucose overloads (2 g/kg). Baclofen pretreatment did not modify GTTs in [GABA.sub.B.sup.-/-] mice, whereas it impaired normal glycemia reinstatement in WT. Baclofen inhibited glucose-stimulated insulin secretion in WT isolated islets but was without effect in [GABA.sub.B.sup.-/-] islets. In [GABA.sub.B.sup.-/-] males, pancreatic insulin content was increased, basal and glucose-stimulated insulin secretion were augmented, and impaired insulin tolerance test and increased homeostatic model assessment of insulin resistance index were determined. Immunohistochemistry for insulin demonstrated an increase of very large islets in [GABA.sub.B.sup.-/-] males. Results demonstrate that [GABA.sub.B]Rs are involved in the regulation of glucose homeostasis in vivo and that the constitutive absence of [GABA.sub.B]Rs induces alterations in pancreatic histology, physiology, and insulin resistance. [gamma]-aminobutyric acid; insulin; glycemia; pancreas histology

Continuous treatment with ivermectin from birth to puberty advanced sexual maturation by 3.7 wk in Holstein heifers grazing pastures naturally infected with nematodes. Every 14 d jugular blood samples were taken from birth to 45 wk of age from all heifers. No differences in serum FSH, estradiol, or thyroxine levels were observed during the trial between the treated and untreated group. Mean LH levels were diminished in untreated heifers 4 wk before the first estrus and the amplitude of LH pulses was augmented in treated heifers when puberty was reached. Serum IGF-I levels increased from birth to 22 wk of age and then reached a plateau in both groups, but levels were consistently higher in treated heifers from 26 wk of age onward. Body weight gain was retarded in parasitized heifers and IGF-I values were positively correlated with body weight only during the first 20 wk of life. We suggest that enhanced prepubertal IGF-I levels in conjunction with increased prepubertal LH levels and pubertal LH pulse amplitude might be involved in the accelerated somatic maturation and in puberty advancement observed in ivermectin-treated heifers. Key Words: Heifers, Puberty, Ivermectin, Gonadotropins, Estradiol, Insulin-Like Growth Factor

The effect of continuous ivermectin treatment from birth to puberty on growth and reproductive performance was studied in Holstein heifer calves grown on pastures in comparison to naturally nematode-infected, untreated animals. Ivermectin effectively abated the presence of nematode eggs in feces. Eggs per gram (EPG) in parasitized animals increased rapidly from wk 12 to 18 of age and then decreased. Animals treated with ivermectin grew faster than untreated ones, and differences in body weight became significant at 6 wk of life, even before eggs appeared in the feces of either treatment group. Ivermectin-treated heifers reached puberty 3 wk earlier than infected ones as assessed with serum progesterone concentrations (ivermectin, 30.4 [+ or -] .8 vs untreated, 33.7 [+ or -] 1.3 wk of age). This delay was not directly related to body weight. In addition, pelvic area at 39 wk and at 15 mo of age was increased in treated heifers (8 and 11%, respectively) compared with parasitized animals. No differences in the wither heights were observed. We conclude that ivermectin treatment in dairy heifers may increase growth rate during development, advance the onset of ovarian function, and positively affect yearling pelvic area. Key Words: Parasitoses, Ivermectin, Puberty, Pelvis, Growth Rate, Dairy Cattle

Background: Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins, and polystyrene and is found in many products. Several reports have revealed potent in vivo effects, because BPA acts as an estrogen agonist and/or antagonist and as an androgen and thyroid hormone antagonist. Objectives: We analyzed the effects of neonatal exposure to BPA on the reproductive axis of female Sprague-Dawley rats. Methods: Female rats were injected subcutaneusly, daily, from postnatal day 1 (PND1) to PND10 with BPA [500 micro g/50 micro L (high) or 50 micro g/50 micro L (low)] in castor oil or with castor oil vehicle alone. We studied body weight and age at vaginal opening, estrous cycles, and pituitary hormone release in vivo and in vitro, as well as gonadotropin-releasing hormone (GnRH) pulsatility at PND13 and in adults. We also analyzed two GnRH-activated signaling pathways in the adults: inositol-triphosphate (IP3), and extracellular signal-regulated kinase 1/2 (ERK1/2). Results: Exposure to BPA altered pituitary function in infantile rats, lowering basal and GnRHinduced luteinizing hormone (LH) and increasing GnRH pulsatility. BPA dose-dependently accelerated puberty onset and altered estrous cyclicity, with the high dose causing permanent estrus. In adults treated neonatally with BPA, GnRH-induced LH secretion in vivo was decreased and GnRH pulsatility remained disrupted. In vitro, pituitary cells from animals treated with BPA showed lower basal LH and dose-dependently affected GnRH-induced IP3 formation; the high dose also impaired GnRH-induced LH secretion. Both doses altered ERK1/2 activation. Conclusions: Neonatal exposure to BPA altered reproductive parameters and hypothalamic- pituitary function in female rats. To our knowledge, these results demonstrate for the first time that neonatal in vivo BPA permanently affects GnRH pulsatility and pituitary GnRH signaling. [ABSTRACT FROM AUTHOR]

GABA has been proposed to inhibit insulin secretion through GABAB receptors (GABABRs) in pancreatic β-cells. We investigated whether GABABRs participated in the regulation of glucose homeostasis in vivo. The animals used in this study were adult male and female BALB/C mice, mice deficient in the GABAB1 subunit of the GABABR (GABAB-/-), and wild types (WT). Blood glucose was measured under fasting/fed conditions and in glucose tolerance tests (GTTs) with a Lifescan Glucose meter, and serum insulin was measured by ELISA. Pancreatic insulin content and islet insulin were released by RIA. Western blots for the GABAB1 subunit in islet membranes and immunohistochemistry for insulin and GABAB1 were performed in both genotypes. BALB/C mice preinjected with Baclofen (GABABR agonist, 7.5 mg/kg ip) presented impaired GTTs and decreased insulin secretion compared with saline-preinjected controls. GABAB-/- mice showed fasting and fed glucose levels similar to WT. GABAB-/- mice showed improved GTTs at moderate glucose overloads (2 g/kg). Baclofen pretreatment did not modify GTTs in GABAB-/- mice, whereas it impaired normal glycemia reinstatement in WT. Baclofen inhibited glucose-stimulated insulin secretion in WT isolated islets but was without effect in GABAB-/- islets. In GABAB-/- males, pancreatic insulin content was increased, basal and glucose-stimulated insulin secretion were augmented, and impaired insulin tolerance test and increased homeostatic model assessment of insulin resistance index were determined. Immunohistochemistry for insulin demonstrated an increase of very large islets in GABAB-/- males. Results demonstrate that GABABRs are involved in the regulation of glucose homeostasis in vivo and that the constitutive absence of GABABRs induces alterations in pancreatic histology, physiology, and insulin resistance. [ABSTRACT FROM AUTHOR]