No abstract

The hypothalamic-pituitary-adrenal axis regulates mammalian stress responses by secreting glucocorticoids. The magnitude of the response is in part determined by gender, for in response to a given stressor, circulating glucocorticoids reach higher levels in female rats than in males. This gender difference could result from estrogen regulation of the corticotropin-releasing hormone (CRH) promoter via either of its receptors: estrogen receptor (ER) ␣ or ER␤. Immunocytochemistry revealed that a subset (12%) of medial parvocellular CRH neurons in the rat hypothalamus contain ER␤ but not ER␣. To determine whether ERs could regulate CRH promoter activity, we cotransfected cells with a CRH promoter construct and either ER␣ or individual ER␤ isoforms. ER␣ weakly stimulated CRH promoter transcriptional activity in a ligand-independent manner. Conversely, all ER␤ isoforms tested stimulated CRH promoter activity with different ligand profiles. ER␤1 and ER␤2␦3 displayed constitutive activity (ER␤1 more than ER␤2␦3). Ligand-dependent activity of ␤ isoforms 1 and 2 was altered by an Exon3 splice variant (␦3) or by the additional 18 amino acids in the ligand-binding domain of ER␤2 isoforms. Lastly, we suggest that ER regulation of CRH takes place through an alternate pathway, one that requires protein-protein interactions with other transcription factors or their associated complexes. However, a pure ER-activator protein-1 alternate pathway does not appear to be involved.

No abstract

Cadmium, mercury, and lead are toxic to humans and animals. Although cadmium and inorganic mercury toxicities occur in humans, they have not been observed in domestic livestock under practical conditions. In contrast, cattle, especially young calves, are extremely susceptible to lead toxicity. Apparently, cattle are more tolerant of cadmium than are other animal species. Due partially to higher absorption and longer retention times in the body, the alkyl mercuries, especially methyl mercury, are more toxic than inorganic mercury compounds. Inorganic forms of cadmium, mercury, and lead are poorly absorbed from the intestine. However, due to lack of effective homeostasis, after absorption retention time is long. Injected cadmium, mercury, and lead are metabolized differently from that naturally absorbed. Most cadmium and mercury are in kidney and liver (50 and 23% of total body in goats); but highest total load of methyl mercury is in muscle (72% in cows). With low to moderate body burden, most lead is retained in the skeleton. However, beyond a certain point, the kidney accumulates large quantities. Only minute amounts of cadmium and mercury are secreted into milk, but milk is only moderately well protected from dietary lead. Likewise, little cadmium and inorganic mercury pass the placental barrier whereas lead and methyl mercury pass more readily.