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The presence of myofibroblasts arranged parallel to the longitudinal axes of anchoring villi of the placenta has previously been described. Furthermore, it has been suggested that intraplacental blood volume, and hence fetal-maternal oxygen-nutrient exchange, may in part be regulated through the longitudinal contraction of anchoring villi. We demonstrate here that anchoring villi have the ability to contract and relax longitudinally. Anchoring villi from normal term human placentae were dissected and suspended from force-displacement transducers to determine their longitudinal contractility in response to potassium chloride (KCl), N(omega)-nitro-l-arginine methyl ester (l-NAME) and the nitric oxide donors sodium nitroprusside (SNP) and glyceryl trinitrate (GTN). Treatment with both KCl and l-NAME resulted in up to a 62% and 74% increase, respectively, in longitudinal contraction over resting tone. In contrast, both SNP and GTN caused a dose-dependent relaxation of precontracted villi. Immunohistochemistry of longitudinal sections of villi confirmed the presence of alpha-actin-containing cells in the extravascular space. Histological staining with hemotoxylin and eosin confirm that the tissue used in these experiments were anchoring villi. These findings suggest that the contraction of anchoring villi may be an important mechanism whereby the placenta may regulate intraplacental volume.

Insulin-induced hypoglycemia inhibits luteinizing hormone (LH) secretion and has been used as a model to study stress-induced inhibition of reproductive function. Endogenous opioid peptides have been implicated in mediating the inhibitory effect of hypoglycemia on LH secretion in sheep and rat. The objective of the present study was to determine if corticotropin-releasing hormone (CRH) and endogenous opiates are involved in the LH response to hypoglycemia in the nonhuman primate. Blood samples were collected at 15-min intervals for 6 h from ovariectomized rhesus monkeys (n = 6). Hypoglycemia was induced by injecting insulin 1 h after initiating blood collection. Animals were pretreated 15 min prior to insulin with either saline (n = 6), naloxone, a nonselective opiate receptor antagonist (n = 4), or alprazolam (n = 6), a potent benzodiazepine which has been shown to inhibit CRH. The LH, glucose, adrenocorticotropin (ACTH), and cortisol responses to insulin were determined. Insulin-induced hypoglycemia significantly inhibited LH secretion and increased ACTH and cortisol concentrations. Alprazolam prevented hypoglycemia-induced inhibition of LH independent of an effect on glucose concentrations. The mean (±SEM) LH pulse interval in response to hypoglycemia was decreased in the alprazolam pretreated group compared to the saline pretreated group (77.4 ± 6.0 vs. 130.0 ± 18.4 min), while LH pulse amplitude and mean LH levels were significantly increased (56.2 ± 7.1 vs. 28.3 ± 5.5 ng/ml, and 105.6 ± 14.4 vs. 60.9 ± 12.1 ng/ml respectively). In contrast, naloxone did not prevent hypoglycemia-induced LH inhibition. The mean LH pulse interval, LH pulse amplitude, and LH concentration in the naloxone pretreated monkeys were 152.1 ± 33.4 min, 37.1 ± 8.9 ng/ml, and 63.7 ± 9.1 ng/ml respectively. Alprazolam pretreatment also markedly attenuated the ACTH response to hypoglycemia whereas the cortisol response was only moderately affected. We conclude that insulin-induced hypoglycemia in the monkey inhibits LH secretion through a mechanism involving CRH but not endogenous opiates.

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Corticotropin-releasing Factor (CRF) is an important inhibitory neuromodulator of GnRH/LH secretion, and mediates in part the inhibitory effects of stress on the hypothalamic-pituitary-gonadal axis. The purpose of the present study was to further investigate CRF's role in regulating LH secretion in primates. This was accomplished by examining LH secretion in ovariectomized rhesus monkeys (n = 7) following cortisol synthesis inhibition with metyrapone. Infusion of metyrapone (5 mg/kg per h) for 4 h decreased cortisol levels to less than 20% of controls while increasing ACTH approximately 10-fold. LH concentrations were not affected by this acute activation of the hypothalamic-corticotroph axis. In a second experiment, metyrapone was infused for 10 h before collecting serial blood samples every 15 min for 6 h. Although this protocol produced a sustained increase in ACTH, no apparent effect on pulsatile LH secretion compared with saline controls was observed. Mean LH (+/- SEM) levels calculated for consecutive 2-h increments were 87.6 +/- 9.2 (0-2 h) 82.1 +/- 5.5 (2-4 h), and 80.7 +/- 4.8 (4-6 h) ng/ml in saline pretreated animals compared with 83.6 +/- 4.9, 79.8 +/- 5.8, and 72.5 +/- 6.2 ng/ml, respectively, in metyrapone pretreated monkeys. The same regimen of metyrapone infusion increased CRF messenger RNA levels in the paraventricular nucleus by approximately 33% (P < 0.0002). In a final experiment designed to examine the potential synergy between CRF and cortisol, the LH response to insulin-induced hypoglycemia was contrasted in saline and metyrapone pretreated monkeys. LH concentrations were reduced to approximately 40% of basal levels following insulin in both metyrapone and saline pretreated monkeys. Therefore, even though inhibition of cortisol synthesis leads to an increase in CRF messenger RNA in the paraventricular nucleus and a robust increase in ACTH secretion in rhesus monkeys, presumably due in part to increased neuroendocrine CRF secretion, LH secretion was not inhibited during either the acute or more chronic phase of corticotroph activation. Absence of LH inhibition was not due to low cortisol concentrations resulting from metyrapone because metyrapone did not prevent hypoglycemia-induced suppression of LH secretion. We conclude that increased neuroendocrine CRF secretion following metyrapone does not inhibit LH secretion under these conditions. Several explanations for this result are discussed.

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