Synaptic remodeling in the arcuate nucleus during the estrous cycle is induced by estrogen and precedes the preovulatory gonadotropin surge.

We have shown that the ovarian cycle is accompanied by a fall in the axosomatic synapses on randomly selected neurons of the arcuate nucleus by the morning of estrus, with a return to the preovulatory levels by the morning of metestrus, indicating a possible role in positive feedback. However, it remains to be proven that the circulating estradiol is the actual regulator of this physiological synaptic plasticity, or that estrogen-induced synaptic retraction precedes in the surge of gonadotropins at midcycle. To resolve these questions, we used an estradiol-immunoneutralization protocol and studied arcuate nucleus axosomatic synapses during the critical points of the estrous cycle. In addition to blocking positive feedback, estrogen immunoneutralization abolished synaptic retraction in the arcuate nucleus. As a positive control, the nonbinding estrogen diethylstilbestrol maintained the gonadotropin surge and synaptic retraction in the antiestradiol-treated animals. Furthermore, in the diluent-treated cycling control females, the synaptic retraction was found to precede the preovulatory LH surge. We demonstrated that the midcycle synaptic retraction of arcuate nucleus synapses is induced by the preovulatory estradiol surge, and that these morphological events precede the preovulatory gonadotropin surge. Taken together, these observations strongly suggest that the hypothalamic mechanism underlying the physiological disinhibition of gonadotropins at midcycle (positive feedback) requires estrogen-induced synaptic retraction in the arcuate nucleus.

Non-specific binding of palytoxin to plastic surfaces.

The changes in blood pressure induced by palytoxin (PTX) administered intravenously through polyethylene (PE) tubing were varied, suggesting either non-specific binding of the toxin to PE or deactivation. By spectrophotometry and HPLC, we found that PTX bound non-specifically to PE tubing and that this binding was attenuated by adding 0.1% rat serum albumin. Furthermore, the chemical stability and activity of PTX were not affected by exposure to room light and/or room temperature. Biological deactivation was excluded as a cause of the observed variability because the hypertensive and lethal effects of infused PTX, delayed with simultaneous administration of sodium nitroprusside (NNP), were in full evidence when the NNP was discontinued 35 min later.

Interaction of cyclic peptides and depsipeptides with calmodulin.

A variety of small peptides bind calmodulin (CaM) and inhibit CaM-dependent enzyme activity. The cyclic peptides cyclosporin A (CSA) and gramicidin-S (GRS) are shown to bind CaM and inhibit 3',5'-cyclic nucleotide phosphodiesterase (PDE) in a calcium-dependent manner. The cyclic peptide microcystin-LR (MLR) and the depsipeptides, valinomycin (VLM) and enniatin-B (ENB), bind to CaM and inhibit PDE activity. Spectral changes exhibited by the binding of MLR, VLM and ENB to dansyl-CaM as compared to that of CSA and GRS reflected different binding sites and/or different conformational changes. The apparent binding constants (Kd) for CaM-peptide were estimated and found to be 4.8 microM for CSA, 2.85 microM GRS, 12.99 microM MLR, 4.29 microM VLM and 41.26 microM ENB. Although these peptides did not inhibit baseline PDE activity, they did inhibit CaM-dependent PDE activity in a dose-dependent manner. Half-maximal inhibition (IC50) of PDE occurred approximately at 0.11 microM MLR; 0.45 microM GRS; and greater than 5 microM for ENB, CSA and VLM. This may be the first observation that these peptides (MLR, VLM and ENB) bind to a known cytoplasmic protein and inhibit an enzyme system dependent on that protein for optimal activity. Interaction of these peptides with CaM may be responsible for creating conformational-functional changes in CaM, thus altering the signal transduction mechanism required for CaM-dependent enzymes, such as cyclic nucleotidase, protein kinases and phospholipase A2.

Peritubular capillaries of the renal cortex in experimental diabetes mellitus in the rat.

Microangiopathy affects the peritubular capillaries in experimental diabetes. Five to six months after streptozotocin administration to induce experimental diabetes in rats, a progressive increase of lymph flow and of the entry of albumin from the renal peritubular capillaries into the interstitium was seen. Under these conditions, owing to the alteration of peritubular physical forces, the uptake of tubular reabsorbate into the capillaries can be impaired with potentially severe consequences in diabetic nephropathy.

Changes in glucose metabolism in premeiotic and meiotic ovaries of the hamster.

The metabolism of glucose changed significantly at the time of the onset of meiosis in the hamster ovary. There was a large drop in the CO2 evolution from labelled glucose and it could be attributed to alterations in the metabolic patterns in the germ cells which represented 80-90% of the ovarian cell population at the time of the studies. The reduced glycolytic metabolism was well established in the oocyte at the diplotene stage of the first meiotic division.

46, XY gonadal dysgenesis with secondary amenorrhea, virilization, and bilateral gonadoblastomas.

A phenotypic girl with secondary amenorrhea, enlargement of the clitoris, XY gonadal dysgenesis, and bilateral gonadoblastomas is described. The presence of secondary amenorrhea does not obviate the existence of a Y chromosome. The presence of the Y chromosome should be a warning that a gonadal tumor may be present and, therefore, gonadectomy must be done as soon as possible and preferably before puberty.

The contribution of the adrenal gland to the total amount of progesterone produced in the female rat.

1. The amount of progesterone contained in both adrenal glands of a rat was similar to or larger than the amount of progesterone in the ovaries of the same rat. This was found in unstressed rats, in stressed rats and also in pregnant rats.2. After ether anaesthesia and exsanguination the adrenal progesterone content was increased by 75%; the ovarian progesterone content remained unchanged.3. In contrast, prolonged operative stress resulted in a rise in the ovarian content of progesterone and 20-dihydroprogesterone whereas the adrenal progesterone content of these rats was lower than that of unstressed rats.4. The rate at which progesterone was secreted by the adrenal glands of stressed rats was similar to the ovarian progesterone secretion rate. Rats which were kept under mild stress conditions before the experiment showed higher adrenal progesterone secretion rates.