Effects of Norethynodrel on the Human Endometrium

Abstract

There has been a constant search for new drugs to treat endocrine disturbances, particularly those of infertility. Norethynodrel,* a 19-nortestosterone derivative, has a unique action on the endometrium. It has been thought to exert a progesterone effect on the human endometrium without estrogenic priming, although it has been uncertain whether all components of the endometrium reacted similarly to this compound.' Revision of our current thinking regarding endocrine metabolism during the menstrual cycle might be necessary if endocrine substances such as norethynodrel should show a selective action on various parts of the endometrium. MATERIALS AND METIIODSFifty-four private patients between 20 and 36 years of age were studied while under treatment for infertility. Ovulation was demonstrated in 15 (control group). Thirty-nine had anovulatory cycles (endometrial biopsies and basal body temperature) and 7 of these had secondary amenorrhea.One patient from the amenorrhea group has been under treatment for 8 months. Endometrial biopsies were obtained from all patients on the twenty-fifth day of the menstrual cycle, before and after treatment. Biopsies were taken from amenorrheic patients immediately before treatment. Thirty-four patients (all groups) were placed on norethynodrel, 10 mg. daily for 10 to 20 days. Twenty mg. daily was given to 20 patients (all groups) for 10 to 20 consecutive days. The medication was started either on the fourth day of the cycle and continued for the next 20 days, or on the twelfth day of the cycle and continued for 10 to 18 days. OBSERVATIONS Normal OvulationFifty-three patients were treated from 1 to 4 cycles.Ten mg. norethynodrel daily f r o m the fourth to twenty-fourth day of the cycle (10 patients). For the most part, the glands were arrested in the early follicular phase, with some showing slight dilatation in patients with normal ovulatory cycles. The glands were lined with either high or low columnar epithelium, with a minimum amount of secretion. The cytoplasm stained poorly.There were some hemorrhagic areas (FIGURES 1 and 2).The response of the endometrium was different when norethynodrel was started a t the mid-cycle. The glands, arrested a t the late proliferative phase, became dilated and cystic. The epithelium was flattened because of the The stroma was cellular, with some edema.T e n mg. daily from the twelfth to thirtieth day of the cycle (5 patients).

Purification of an Ion-Stimulated Adenosine Triphosphatase from Plant Roots: Association with Plasma Membranes

“…3), and stelar parenchyma (Fig. 4) cells were specifically stained by PACP, a stain that is known to be specific for plasma membranes in plants (18,(27)(28)(29). No other cell membranes were stained with PACP (compare Fig.…”

“…Lipids were extracted from membrane fractions and washed according to Folch et al (22). Lipid-P was determined by the procedure of Rouser et al (23), and total sterols were determined as described by Stadtman (24 with lead citrate or with PACP, which preferentially stains plasma membranes of plants (18,(27)(28)(29).…”

“…In addition, the isolated membranes were stained with PACP (a special stain consisting of periodic acid, chromic acid, and phosphotungstic acid; see refs. 18,[27][28][29], which specifically stained oat-root plasma membranes in situ. These results provide the first evidence that the plant-root ATPase, which is stimulated by monovalent ions, is associated with the plasma membrane, and this finding serves to further implicate the enzyme in the absorption of inorganic ions by plant roots.…”

Metabolism of the synthetic progestogen norethynodrel by human ketosteroid reductases of the aldo–keto reductase superfamily

“…The use of NOR in contraceptives is based on its progestational properties. However, NOR is also known to exert estrogenic effects [5, 6]. It is possible that the metabolites contribute to, or even, are responsible for the pharmacological effects of the parent compound.…”