Mechanism of luteolysis: effect of estradiol and prostaglandin F2 alpha on corpus luteum luteinizing hormone/human chorionic gonadotropin receptors and cyclic nucleotides in the rhesus monkey.

Recent studies from our laboratory suggest that estrogen-induced luteolysis in the primate may be mediated through synthesis of prostaglandin F2 alpha (PGF2 alpha). To elucidate further the mechanism of luteolysis, normally cycling rhesus monkeys received intra-corpus luteum (CL) injections of estradiol (100 microgram), PGF2 alpha (500 microgram), or the appropriate vehicles on the seventh day after the preovulatory estradiol surge. Peripheral vein blood was drawn, at 30-minute intervals for 6 hours for progesterone and luteinizing hormone (LH) assays. Five hours after intra-CL injection, the CL was excised and the LH/human chorionic gonadotropin (hCG) receptor-binding activity and cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) were measured. PGF2 alpha significantly (p < 0.05) lowered progesterone within 1 hour, while the time required for estradiol to lower progesterone significantly was 3.5 hours; there was no significant change in LH, Estradiol and PGF2 alpha significantly (p < 0.05) decreased the LH receptor-binding capacity at 5 hours, without any change in the binding affinity. Also PGF2 alpha significantly (p < 0.05) increased cGMP in the CL, while cAMP remained unchanged; estradiol treatment resulted in a significant (p < 0.05) increase in cAMP with no change in cGMP. This study suggests that estradiol and PGF alpha cause a decrease in progesterone secretion by a loss of the LH/hCG receptor and the PGF2 alpha may act further through the cGMP system.

The relationship of changes in mammary blood flow and plasma progesterone at the time of parturition in the ewe.

Previous studies indicate that there is a fall in maternal plasma progesterone and a marked increase in mammary blood flow (MBF) at the time of parturition in ewes. In this experiment the role of progesterone as a cause of this increase in MBF was investigated. Progesterone was infused (9.9 mcg. per minute) into a branch of the mammary artery in five sheep during the induction of premature labor by fetal dexamethasone infusion (1 mg. per 24 hours) to prevent the normal fall in concentration of local mammary artery progesterone. Five ewes used as controls received a mammary artery infusion of cholesterol (9.9 mcg. per minute). In the cholesterol-infused group MBF increased significantly from baseline after 13 +/- 4 hours (mean +/- standard error) to a peak flow of 235 +/- 9 ml. per minute. In the group receiving the progesterone the increase in MBF was delayed to 35 +/- 7 hours, reaching only 161 +/- 22 ml. per minute. These results were significantly different from control group results (p less than 0.01). This study suggests that the fall in maternal plasma progesterone which occurs at the time of parturition may play a role in the increase in MBF that occurs prior to the onset of labor, delivery, and lactogenesis.

Examination of the filterability of oxygenated erythrocytes (containing normal, trait or sickle cell disease type hemoglobins) in the presence of L-epinephrine, D,L-isoproterenol or prostaglandins (PG) A1, A2, E1, E2, F1alpha or F2alpha.

These studies were directed toward determining effects of selected vasoactive compounds on oxygenated erythrocytes. Considering the major circulatory effects that small changes in blood flow might initiate in sickle cell anemia patients, erythrocytes from individuals with this disease and from one person with the trait condition were included. PGA1, PGE1, and PGE2 significantly increase filtration times in normal erythrocytes (AA-type hemoglobin) at 10(-11) M by this method. From studies of the effects of L-epinephrine, D,L-isoproterenol, PGA1, PGA2, PGE1, PGE2, PGF1alpha and PGF2alpha on red blood cell filterabilities, the following observations and conclusions appear to hold: (1) Erythrocytes from different individuals (or from the same individual at different times) vary greatly in responses to these compounds. Effects of vasoactive compounds upon red cell filterability may be positive, negligible or negative. Decreased filterability (positive effect) was seen more frequently than increased. (2) Effects are observed with all compounds on some erythrocyte preparation at every concentration tested (10(-5), 10(-7), 10(-9), 10(-11) M). (3) Where epinephrine showed significant positive effect, PGA2 and PGE2 did also when tested. The reverse was not always true. (4) For PGA and PGE analogs, the subscript 2 analogs affected filterability more frequently. (5) When significant average effects for a group of donors were produced by a given compound at a particular concentration, these effects were positive for the donors studied.