Ch.V. Rao

Previous studies have suggested that activation of normal human adrenal and adrenal tumor luteinizing hormone (LH)/chorionic gonadotropin (hCG) recep

Bovine oviductal epithelium contains LH receptors, which function in the increase of synthesis of oviductal glycoprotein (OGP). As with cocultures of

PROBLEM: To determine whether macrophages in human reproductive tissues contain luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor mRNA and receptor protein that can bind ¹²⁵I‐hCG.METHOD OF STUDY: Macrophages isolated from term pregnancy human decidua were used for LH/hCG receptor detection by in situ hybridization for receptor mRNA and immunocytochemistry for a macrophage marker, CD68, performed alone and in combination, reverse transcription‐nested polymerase chain reaction, Western and ligand blotting. The LH/hCG receptor presence in macrophages in late luteal phase human endometria and corpora lutea was determined by sequential performance of in situ hybridization and immunocytochemistry.RESULTS: The macrophages present in term pregnancy human decidua and late luteal phase human endometria and corpora lutea contain LH/hCG receptors.CONCLUSIONS: This is the first demonstration of macrophages present in human reproductive tissues containing LH/hCG receptors. The receptor presence suggests that LH and hCG may regulate macrophage functions in gonadal as well as in non‐gonadal target tissues.

Cushing's syndrome occurring during pregnancy is frequently due to an adrenal neoplasm. Adrenal gland tumors occasionally respond to luteinizing hormone (LH) or human chorionic gonadotropin (hCG). We report a case of Cushing's syndrome during and following pregnancy due to an adrenal carcinoma which expressed the LH/hCG receptor. The presence of these receptors may have led to the growth and function of the tumor during pregnancy.

Leptin, protein product of the ob gene, not only regulates food intake and energy expenditure but also has a number of other actions in the body. Leptin actions are mediated by its receptors that have either a long or a truncated intracellular domain, which is coupled to signal transduction pathways. Previous studies have demonstrated that human placenta expresses both leptin and its receptors. However, it is not known whether human umbilical cord and fetal membranes are also sites of expression of these molecules. Therefore, the present study investigated leptin and its receptor expression in these tissues from term pregnancy. Reverse-transcription polymerase chain reaction (RT-PCR) amplified expected size fragments of leptin and also its short and long receptor isoforms from umbilical cord and fetal membranes. The authenticity of PCR-amplified fragments was confirmed by Southern blot hybridization with corresponding cDNA probes. Western blotting revealed that the transcripts were translated into 16-kDa leptin, and 125-kDa (long) and 100-kDa (short) leptin receptor isoforms. However, the long form is present in umbilical cord and the short form in the fetal membranes. Immunocytochemistry revealed that leptin and its receptor isoforms were present in endothelial cells and smooth muscle of umbilical veins and artery, myofibroblasts in Wharton's jelly, amnion covering the cord, amnion and chorion in reflected fetal membranes and decidua from membranes. Amnion, however, contained the highest levels of leptin and its receptor immunostaining. In summary, term pregnancy human umbilical cord and fetal membranes co-express leptin and its receptor genes, which supports the hypothesis that leptin is an autocrine and paracrine regulator in these tissues.

Recent studies found that human and animal breast tissues and human breast cell lines contain low levels of receptors that bind hCG and its structural and functional homologue, LH. Those gonadotropins exert numerous anticancer effects in breast cancer models and cells, which might explain decreased breast cancer incidence in women who complete full-term pregnancies at a young age. The new findings also imply that premature chronic elevations of LH levels might contribute to decreased breast cancer incidence in women with early menopause, and elevated LH levels might contribute to a better prognosis after ovariectomy. Those findings predict that breast cancer risk might be reduced by early hCG treatment of women who plan to delay their first pregnancies; prophylactic hCG treatment might help women with family histories of breast cancer or oncogene mutations that predict breast cancer; and better prognoses might result when hCG is administered to breast cancer tissue.

Steroidogenic factor-1 (SF-1) is a member of an orphan nuclear hormone receptor superfamily. It plays a critical role in the development and function of the hypothalamic–pituitary–gonadal and adrenal axis. However, whether SF-1 can regulate transcription of gonadotrophin-releasing hormone (GnRH) gene is not known. To examine this possibility, we first over-expressed SF-1 and found that it not only decreased steady state GnRH messenger ribonucleic acid (mRNA) levels but also reduced its promoter activity in GT1-7 neurons. The inhibitory effect of SF-1 was lost when the 5′-flanking region of GnRH gene containing two distal (-1479 to –1474 bp and –1059 to –1054 bp) hexamers was deleted. Gel mobility shift assays showed that GT1-7 cell nuclear extracts contained a protein that formed a specific complex with synthetic oligonucleotides containing the two distal hexamers or a consensus SF-1 binding sequence. The migration of this complex was, however, slower than the complex formed with MA-10 cell nuclear extracts which were shown to contain a 53 kDa SF-1 protein. The addition of anti-SF-1 antibody supershifted the complex formed with MA-10, but not with GT1-7 cell nuclear extracts. The same antibody, however, detected a 60 kDa protein and immunostained nuclei of GT1-7 neurons. These results are consistent with GT1-7 neurons containing an SF-1-like protein that can bind to the distal hexamer sequences in the 5′-flanking region of rat GnRH gene to inhibit its transcription.