Theresa M. Siler-Khodr

Temporal relationships of estrogen, progesterone, and luteinizing hormone levels to ovulation in women and infrahuman primates

These studies were undertaken to ascertain the interval between the estrogen and LH peaks and ovulation in women, rhesus monkeys, and baboons. Estrogen, progesterone, and LH were measured by RIA. Ovulation was documented by visual examination of the ovaries, histology of the corpora lutea, and recovery of ova. The data for human subjects was based on a group of 23 normal women scheduled for surgical sterilization. Blood was drawn daily between 8:30 and 10:30 P.M. beginning on day 10 of the cycle. Surgery was performed 1 to 5 days after the LH peak. The hormonal findings were correlated with the histology of the corpus luteum. The mean interval from the estrogen peak to ovulation was 34 hours, the interval from the estrogen peak to the LH peak was 24 hours, and that from the LH peak to ovulation was 9 hours. In 46 rhesus monkey cycles and in 53 baboon cycles diagnostic serial laparoscopic examinations were initiated following the estrogen peak and repeated every 24 hours until ovulation was confirmed. The mean interval between the estrogen peak and ovulation was 34 hours in the monkey and 41 hours in the baboon. The intervals from the estrogen peaks to the LH peaks were 12 hours in the monkey and 23 hours in the baboon. The intervals from LH peak to ovulation were 22 hours in the monkey and 18 hours in the baboon. Plasma progesterone levels were significantly increased prior to the LH peak in all three species.

Normal values of urinary albumin and total protein excretion during pregnancy

OBJECTIVE Our purpose was to determine the normal 24-hour excretion values of urinary albumin and total protein in healthy pregnant women. STUDY DESIGN We evaluated 270 healthy pregnant women < or = 35 years old without a history of diabetes, hypertension, pyelonephritis, preeclampsia, or renal or connective tissue disease. Adequacy of 24-hour collection was determined by creatinine excretion. RESULTS The mean protein excretion in 24 hours was 116.9 mg, upper 95% confidence limit 259.4 mg. The mean albumin excretion in 24 hours was 11.8 mg, upper 95% confidence limit 28.7 mg. Both protein and albumin excretion increased after 20 weeks of gestation. No patient had evidence of microalbuminuria, defined as urinary albumin excretion > 30 mg/L. CONCLUSION These data support 260 mg per 24 hours of urinary protein and 29 mg per 24 hours of albumin as the upper limit of normal in pregnancy. Albumin accounts for a small fraction of total urinary protein excretion.

The Effect of Luteinizing Hormone-Releasing Factor on Human Chorionic Gonadotropin Secretion

The effect of luteinizing hormone-releasing factor (LRF) on secretion of human chorionic gonadotropin (hCG) by the human placenta in culture was studied. A specific stimulation of hCG secretion was observed. The stimulation of hCG production correlated with the LRF dose in the culture medium. On the other hand, the secretion of human chorionic somatomammotropin was not affected. These data demonstrate a specific action of LRF on placental production of hCG in vitro.

Localization of Luteinizing Hormone-Releasing Factor in the Human Placenta

Luteinizing hormone-releasing factor (LRF) has been found to be produced by the placenta. In the present study, the localization of this releasing factor was delineated by the use of an immunofluorescnece technique. Intense fluorescence was localized in the cytotrophoblast, along the outer surface layer of the syncytiotrophoblast, and in the villous stroma. The cytoplasm of the syncytiotrophoblast did not exhibit any fluorescence. It may be speculated that placental LRF plays a role in regulating the production of human chorionic gonadotropin.

Inhibition of hCG, αhCG and progesterone release from human placental tissue in vitro by a GnRH antagonist

A dramatic suppression of hCG, alpha hCG and progesterone release from midgestation, human placentas in vitro was effected when incubated with 1 microgram/ml of an antagonist to GnRH. This inhibition of hormonal release occurred rapidly and was partially restored by the addition of GnRH. Human chorionic somatomammotropin was also suppressed, but only two days following the decline of the other hormones. These data demonstrate that an antagonist to GnRH can rapidly inhibit human placental hormone release.

Interactions of Pinealectomy and Short-Photoperiod Exposure on the Neuroendocrine Axis of the Male Syrian Hamster

The effect of pineal gland removal on neuroendocrine function of male Syrian hamsters housed under long (14 h light:10 h dark) or short (5 h light 19 h dark) photoperiod conditions was tested. In sham-operated, but not in pinealectomized, animals, exposure to the short photoperiod resulted in a significant reduction in testicular weight. Median eminence (ME), medial basal hypothalamus (MBH), and medial preoptic-suprachiasmatic (MPOA-SCN) norepinephrine (NE) turnover was significantly reduced in 5 L:19 D sham-operated animals as compared to 14 L:10 D sham-operated or 14 L:10 D pinealectomized controls. The effects of short photoperiod on ME and MPOA-SCN NE turnover were reversed by pinealectomy, but reductions in MBH NE turnover were not dependent on the presence of the pineal gland. Pineal-dependent decreases in MBH and increases in MPOA-SCN dopamine turnover were also observed after transfer of hamsters from long to short photoperiods. Both ME and MBH luteinizing hormone-releasing hormone (LHRH) levels were increased after short-photoperiod exposure, but pineal removal prevented these increases of LHRH levels only in the MBH of the 5 L:19 D hamsters. Levels of serotonin or its metabolite, 5-hydroxyindole-acetic acid, were not affected by pinealectomy and/or short-photoperiod exposure. We conclude that short-photoperiod-induced gonadal atrophy in the Syrian hamster is associated with pineal-dependent and pineal-independent changes in hypothalamic neurotransmitter turnover and hypothalamic LHRH content.

Immunoreactive gonadotropin-releasing hormone level in maternal circulation througout pregnancy

Immunoreactive gonadotropin-releasing hormone was quantitated in maternal blood. Circulating levels of gonadotropin-releasing hormone were found to be significantly higher during pregnancy than in nonpregnant cycling women. The highest concentrations of gonadotropin-releasing hormone immunoreactivity were observed in the first half of pregnancy with values at 20 to 42 weeks being significantly lower. A correlation with placental human chorionic gonadotropin-releasing hormone concentrations and maternal circulating gonadotropin-releasing hormone levels was noted. Four pregnancies that resulted in premature labor and/or delivery had very low circulating maternal gonadotropin-releasing hormone concentrations, possibly reflecting placental dysfunction in these cases.

Effects of estrogen-induced hyperprolactinemia on endocrine and sexual functions in adult male rats

Chronic estrogen treatment can lead to development of prolactin (PRL) secreting pituitary tumors. We have tested the ability of diethylstilbestrol (DES) to produce persistent hyperprolactinemia (hyperPRL) in adult male rats and examined the effects of this treatment on hypothalamic-pituitary-testicular function, adenohypophyseal structure, copulatory behavior and fertility. Silastic capsules containing approximately 5 mg DES were subcutaneously implanted into adult male CDF (F-344)/CrlBR rats and removed 15 or 20 weeks later. Extreme hyperPRL, as well as suppression of plasma LH and FSH levels, persisted after DES capsules were removed. In contrast, plasma testosterone levels increased rapidly after removal of DES capsules and reached normal levels within 4-6 weeks. Copulatory behavior was assessed on two occasions between 7 and 14 weeks after removal of the DES capsules and was found to be suppressed in DES-treated rats, as evidenced by significant increases in latencies to mount, to intromit and to ejaculate. Moreover, when the animals were placed with normal females, the interval until conception was significantly greater in DES-treated than in control males. In spite of these differences in copulatory behavior, 10 of 11 DES-treated males were fertile. At autopsy, 44 weeks after capsule implantation (i.e. 24 or 29 weeks after capsule removal), DES-treated rats had marked enlargement of the anterior pituitary, increased weights of the lateral prostate and the adrenals, increased levels of testicular hCG-binding sites, reduced concentration of dopamine and norepinephrine in the median eminence and increased concentration of LHRH in the preoptic area.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of treatment with gonadotropin-releasing hormone analogues on pregnancy outcome in the baboon * †

The effect of a gonadotropin-releasing hormone (GnRH) agonist, Zoladex (Imperial Chemical Industries, PLC, London, England), and an antagonist, Organon 30276 (Organon, Oss, Holland), on the outcome of pregnancies when administered just after implantation was examined. The antagonist, Organon 30276, was administered continuously from days 14 through 21, and the agonist, Zoladex, was injected as long-acting pellets on day 14 after conception to pregnant baboons. Maternal baboon chorionic gonadotropin and progesterone levels and sonographic measurement were made before, during, and after treatment and throughout pregnancy of control and treated animals. Two pregnant animals were treated with 3.6 mg of Zoladex; one aborted and one had a stillbirth. Another four pregnant baboons were treated with 7.2 mg of Zoladex; two aborted, one had a premature with a low-birthweight infant, and one had a normal liveborn. Organon 30276, at 50 mg, was administered to three pregnant baboons and resulted in one stillbirth, one neonatal death, and one normal liveborn. The two pregnant baboons treated with 100 mg Organon 30276 both aborted. Therefore, treatment with these GnRH analogues in very early baboon pregnancy could adversely affect the outcome of pregnancy. Thus attention should be paid to the possible presence of early pregnancy at the time of GnRH analogue therapy, which might adversely affect the outcome of the pregnancy.

Extrahypothalamic Luteinizing Hormone-Releasing Factor (LRF): Release of Immunoreactive LRF in Vitro *

The human placenta in vitro releases luteinizing hormone-releasing factor (LRF) which is immunologically indistinguishable from hypothalamic LRF. The release of LRF by placental tissue increased during the 4 days of culture and exceeded the original tissue content more than 5-fold. These data suggest that the human placenta may synthesize an LRF molecule immunologically identical with hypothalamic LRF.