No description available.

No description available.

Both estradiol and progeterone are proposed autocrine or paracrine regulators of ovarian function in primate species. However, specific receptors for these steroids have not been localized to individual compartments of the primate ovary. Using immunocytochemical techniques, estradiol receptors were detected in the germinal epithelium, but not other structures, of ovaries obtained from rhesus or cynomolgus monkeys during the follicular and luteal phases of the menstrual cycle. In contrast, progesterone receptors were present in stromal and interstitial tissue, the thecal layers of healthy and atretic follicles, as well as the functional corpus luteum. These results are consistent with the concept of a receptor-mediated role for progesterone, but not estrogen, within the predominant gametogenic and endocrine structures, e.g., the follicle and corpus luteum, of the primate ovary. The recent discovery of distinct cell types in the corpus luteum of domestic ungulates has revised concepts on the control of luteal function in these species. Studies were designed to test the hypothesis that the primate corpus luteum consists of cell subpopulations that differ in physical characteristics, function and regulation. Cells enzymatically-dispersed from the monkey corpus luteum at mid-luteal phase of the menstrual cycle differed in size (diameter) and the presence of the steroidogenic enzyme, 3β-hydroxysteroid dehydrogenase (3β-HSD). Analysis of dispersed cells for forward and 90° light scatter properties by flow cytometry revealed two distinct continua (Cα and Cβ). These continua were isolated using the sorting capabilities of the flow cytometer. Cα contained single cells of ≤ 15 μm and cell clusters; the cells were typically 3β-HSD-negative nonsteroidogenic. Cβ consisted of single cells that increased in size up to 40 μm and were 3β-HSD-positive. Cβ was divided into two regions (R₁ and R₃) and the cells isolated. R₁ cells were ≤ 15 μm whereas R₃ cells were ≥ 20 μm. Basal progesterone and estrogen production by R₃ cells was greater than that produced by R₁ cells (as determined by radioimmunoassay of the incubation media). Relative stimulation of progesterone production by hCG, cAMP or PGE₂ was not different between R₁ and R₃ luteal cells. These results support the hypothesis that the primate corpus luteum consists of distinct cell subpopulations which differ in size and steroidogenic capacity. However, the cell types which secrete progesterone are typically responsive to gonadotropin and PGE₂, possibly via a cAMP-mediated pathway.

Alpha-melanotropin (alpha-melanocyte stimulating hormone, α-MSH) exerts its biological action by binding to specific receptors on the outer cell membranes of its target tissues with a high degree of affinity and specificity. Current evidence suggests that this takes place both in vitro and in vivo in both normal and malignant melanocytes. Thus, if it were possible to attach a radioisotope (e.g., ¹²⁵I) to α-MSH, or a suitable analogue, without interfering with the receptor affinity of the hormone, then a radioreceptor assay could be developed which would allow hormone-receptor interaction to be studied in detail. In addition, this radio-labeled melanotropin might be expected to accumulate in melanoma tumors in vivo thus facilitating tumor localization by nuclear imaging methods as has been successfully accomplished for thyroid tumors. The present studies were initiated to develop a radioactive melanotropin with full, or nearly full, biological activity. This labeled melanotropin must be of sufficient specific radioactivity to be suitable as a tracer in a radioreceptor assay and ultimately as a marker for in vivo tumor localization. The studies described herein provide information concerning: chloramine T induced iodination, lactoperoxidase catelyzed iodination, and iodogen induced iodination of α-MSH and certain structural analogues. Radio-labeled derivatives of various melanotropins were prepared using a variety of iodination techniques. Under conditions commonly used for the iodination of other peptides a substantial loss of biological activity of the native hormone (α-MSH) was observed. This loss of hormonal activity was primarily a consequence of oxidation of methinonine and occurred regardless of the oxidant used (chloramine T, lactoperoxidase-hydrogen perioxide, or iodogen). Under similar iodination conditions using 4-norleucine-alpha-melanotropin ([Nle⁴]-α-MSH), satisfactory incorporation of label into the peptide was accomplished without significant loss of biological activity. Data are presented suggesting that this peptide is far superior to α-MSH for use in the preparation of a radioactive melanotropin. Although some success was achieved using [Nle⁴]-α-MSH with all three iodination methods, the simplest and most consistent method involved the use of iodogen followed by purification of the labeled product using high performance liquid chromatography (HPLC). This importance of these studies in the development of a tracer for a radio-receptor assay and for in vivo localization of melanoma tumors is discussed.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.