Consequences of endocrine disrupting chemicals on reproductive endocrine function in birds: establishing reliable end points of exposure.

It has been difficult to establish reliable indices of exposure to endocrine disrupting chemicals (EDCs) appropriate for a variety of avian species because of a vast array of reproductive strategies. Data from mammals, reptiles and fish provide insight on likely mechanisms of action for EDCs. However, many of the effects of EDCs are weaker than the actions of the native hormones, making it difficult to assess adverse effects in domestic and wild birds. It is clear that differential sensitivity to EDCs exists across species, due to the timing and mode of exposure, compound toxicity and age of the individual. Our studies on EDCs are conducted in the quail model system, with focus on reproductive endocrine, neuroendocrine and behavioral responses. Studies have included EDC exposure, either by egg injection or via diet. Results from egg injection studies showed the following: (1) estradiol administered by embryonic day 12 demasculinized male sexual behavior, altered hypothalamic neurotransmitters and reduced hen day production and fertility in a dose dependent fashion, (2) methoxychlor (MXC) or vinclozolin impaired male sexual behavior in adult quail and (3) DDE exposure impaired reproductive and immune related end points. Two-generation studies were conducted on Japanese and northern bobwhite quail with dietary methoxychlor (MXC) exposure (0, 5 and 10 ppm) beginning in adults (P1), continuing in their offspring (F1), with F2 offspring raised on control diet. MXC exposure impaired male sexual behavior, hypothalamic catecholamines and plasma steroid hormones. Moreover, MXC exposure had reproductive consequences observable at both the lower and higher doses of MXC in F1 and F2 generations. These data demonstrate that embryonic EDC exposure interferes with sexual differentiation of neural systems that direct reproduction.

Premenstrual syndrome and related hormonal changes. Long-acting gonadotropin releasing hormone agonist treatment.

The results of long-acting, injectible gonadotropin releasing hormone agonist (GnRH-a) and placebo treatment of severe premenstrual syndrome (PMS) patients with regular menstrual cycles and without known psychiatric disorders are reported. Diagnosis was made according to the Menstrual Symptom Questionnaire and Menstrual Symptom Diary scores. In a placebo-controlled, crossover study, 12 subjects were given either normal saline or depot leuprolide acetate (7.5 mg) every 30 days, starting with the onset of menses. Each subject received the same agent twice before switching to the other and did not known which agent was given. A significant decrease in PMS symptoms was reported by all subjects in both treatment regimens. Biweekly venous blood sampling showed significant elevations of beta-endorphin levels and suppression of gonadotropin concentrations in subjects receiving depot leuprolide treatment. Short-term treatment of severe PMS with an injectible, long-acting GnRH-a may not treat the disease more than do saline injections in a group of women selected by certain criteria.

Clinical nurse specialist subroles: foundations for entrepreneurship.

Entrepreneurship is a career option for nurses seeking autonomy in their practice. The six subroles of the CNS--researcher, consultant, advanced clinician, educator, leader/manager, and collaborator--provide the framework for discussion of the functional aspects of this new option. Examples demonstrate how these subroles have been used by various nurse entrepreneurs. Implications for practice and recommendations are provided.

Gonadotropin and ovarian hormone dynamics in luteal phase defects.

Blood samples were obtained during early follicular, periovulatory, and luteal phases in four women with out-of-phase endometrial biopsy specimens and four normal controls. In the study cycle, follicular development was evaluated and a late luteal phase endometrial biopsy was performed in each subject. Area under the luteal phase progesterone curve positively correlated with degree of maturity of the endometrial biopsy. Peak serum estradiol, maximum follicular diameter, and both immunoactivity and bioactivity of the preovulatory luteinizing hormone and follicle-stimulating hormone surges were similar in the luteal phase defect cycles as compared with normal cycles. Likewise luteinizing hormone bioactivity in the luteal phase of the luteal phase defect cycles was similar to that of normals. These data show that the immunoactivity and bioactivity of periovulatory and luteal phase gonadotropins may be normal in luteal phase defect cycles.

Effects of 17-hydroxyprogesterone caproate (17-OHPC) administration to pregnant squirrel monkeys (Saimiri boliviensis boliviensis).

Poor reproductive performance of the squirrel monkey (Saimiri boliviensis boliviensis) in captivity and a relative progesterone (P) deficiency in pregnancy have been reported. Since premature births may contribute to pregnancy wastage, we attempted to measure the effectiveness of 17-hydroxyprogesterone caproate (17-OHPC) treatment of pregnant squirrel monkeys to prevent early deliveries. Based on clearance studies of nonpregnant animals, 25 mg of 17-OHPC was administered at 6-day intervals to a test group of 31 pregnant monkeys while the control group of 29 received saline. Venous blood was obtained at 6- to 12-day intervals for measurement of 17-hydroxyprogesterone (17-OHP), P, 17-B estradiol (E), and androstenedione (A), and dihydroepiandrosterone (DHEA) levels by radioimmunoassays. The treated group had a significant increase in serum 17-OHP (P < 0.001), P (P < 0.01), and DHEA (P < 0.05) levels compared to controls. The numbers of live births, stillbirths, or neonatal deaths did not differ significantly between groups. Although 17-OHPC administration appeared to increase P and 17-OHP levels, this did not alter the duration of pregnancy nor delay the onset of labor. A significant fall in 17-OHP, P, and E levels was observed 6-12 days before delivery.

The effect of aging on hypothalamic function in oophorectomized women.

To detect age-related changes intrinsic to hypothalamic-pituitary function, we studied plasma gonadotropin levels in 12 oophorectomized women ages 27 to 64 years who were not undergoing hormone replacement therapy. Blood drawn from an indwelling catheter every 10 minutes for 5 hours was assayed for follicle-stimulating hormone, luteinizing hormone, estradiol, and prolactin concentrations. All estradiol levels were less than 20 pg/ml and prolactin values were normal. Mean gonadotropin concentrations, pulse frequency, and pulse amplitude were no different in women aged 27 to 49 years as compared with subjects 52 to 64 years old. When grouped according to gynecologic age (years since puberty) or years after oophorectomy, luteinizing hormone and follicle-stimulating hormone mean concentrations, mean pulse frequency, and mean pulse amplitude were comparable to those grouped according to chronologic age. On the basis of our findings, lack of response from postmenopausal ovaries to endogenous gonadotropin stimulation is a result of primary age-related change in the ovary, not in the hypothalamus.

Variations in c-fos gene expression during rat brain development.

Expression of the c-fos proto-oncogene has been associated with mitosis or differentiation in a number of tissue culture model systems. We have studied the expression of this gene during in vivo brain development in the rat. Our results demonstrate that very low levels of c-fos mRNA are detectable during the period of development characterized by rapid mitosis, whereas much higher concentrations of c-fos mRNA are found in the brains of older neonatal animals and adults. Therefore, although c-fos could be participating in the regulation of mitosis during early postnatal development of the brain, it is also likely to play an important role in mature brain tissue.

Serum oestradiol, progesterone, chorionic gonadotrophin and prolactin concentrations during pregnancy in the Bolivian squirrel monkey (Saimiri sciureus).

Concentrations of chorionic gonadotrophin gradually increased during early pregnancy, reached maximum values at mid-gestation, then declined to low levels. Oestradiol-17 beta concentrations were relatively low (300-600 pg/ml) during early pregnancy, increased thereafter to high levels (10-35 ng/ml), and then appeared to decline towards term. Concentrations of progesterone were constant (100-200 ng/ml) for the first 15 weeks of gestation, suggesting that sequential measurements of progesterone could be used to diagnose early pregnancy. Prolactin concentrations rose during pregnancy, reaching maximum values at term.

Serum hormone patterns during abortion in the Bolivian squirrel monkey.

Serum measurements of chorionic gonadotropin (CG), estradiol (E-2) and progesterone (P) were used to describe patterns of hormonal change in Bolivian squirrel monkeys undergoing spontaneous abortion. During early pregnancy, serum CG levels gradually increased, reaching maximum levels at the end of the first 50 days of pregnancy (range: 200-1964 ug protein/ml). E-2 concentrations also increased to high levels (10-30 ng/ml) toward the end of pregnancy, while serum P remained fairly constant at levels above 100 ng/ml. A gradual decline in serum hormone concentrations was observed in aborting animals. CG levels declined to less than 100 ug protein/ml while E-2 and P decreased to concentrations characteristic of nonpregnant cycling animals, less than 500 pg/ml and 20 ng/ml respectively. The data suggest that two weekly measurements of CG and E-2 could be used to identify monkeys undergoing abortion and those which have already aborted.

Progesterone as a predictor of cyclicity in Bolivian squirrel monkeys during the breeding season.

In a squirrel monkey breeding colony, two distinct groups of females were observed during the breeding season, December through March. One had low and the other had high estradiol (E2) and progesterone (P) concentrations. The conception rate in females with high E2 and P values was 74%. However, only 25% of monkeys with low steroid concentrations became pregnant during the breeding season. This study showed that all mature females in a colony may not be cycling concurrently and that two serum P measurements obtained at four-day intervals may be utilized to detect noncycling monkeys during the breeding season.