Episodic variations of prolactin, thyroid-stimulating hormone, luteinizing hormone, melatonin and cortisol in infertile women with subclinical hypothyroidism

Preliminary data have suggested that female infertility due to corpus luteum insufficiency may be caused by subclinical hypothyroidism [exaggerated thyroid-stimulating hormone (TSH) response to thyrotrophin- releasing hormone (TRH) stimulation]. L-Thyroxine supplementation has been recommended to achieve pregnancies in subclinical hypothyroid women. This controlled study was carried out in order to investigate the biochemical diagnosis of subclinical hypothyroidism as a possible infertility factor. Five infertile patients (aged 25-36 years) with subclinical hypothyroidism (n = 4, stimulated TSH >20 microU/ml) or primary hypothyroidism (n = 1) and five healthy controls (aged 22-39 years) with normal thyroid function (stimulated TSH <15 microU/ml), regular cycles and no history of infertility were studied in the early follicular phase. In the pre-study evaluation, eight of 23 volunteers (34.8%) had to be excluded because of subclinical hypothyroidism with stimulated TSH values (TSHs) >15 microU/ml. Cycle function of patients and controls was compared by the method of LH pulse pattern analysis. Therefore blood samples were drawn every 10 min during a 24 h period. Sleep was recorded from midnight to 7 a.m. Repetition of the TRH tests at the end of the 24 h blood sampling period confirmed the difference in stimulated TSH values of the two study groups. Pulse analysis for luteinizing hormone (LH), TSH and prolactin showed no differences between patients and controls for pulse frequency, amplitude, height, length, area under curve (AUC) and the 24 h mean. Even the hypothyroid patient had a normal LH pulse pattern. Additional measurement of melatonin in pooled sera every 30 min gave the well-documented diurnal profiles during day and night for both groups. Patients had significantly higher melatonin values at seven time points during the night. Peaks for LH, TSH, prolactin and cortisol were correlated with the sleep stages wake, rapid eye movement, 1 + 2 and 3 + 4. We concluded that corpus luteum insufficiency in female infertility cannot be explained by subclinical hypothyroidism and thus should not be treated with L-thyroxine for fertility reasons.      

Evidence for pH-induced release of RNA from belladonna mottle virus and the stabilizing effect of polyamines and cations

The RNA of belladonna mottle virus (BDMV) is released from virions by increasing the pH to neutrality or above, leaving behind intact protein shells. In contrast, much harsher conditions are required to release the RNA from the closely related turnip yellow mosaic virus (TYMV). The heat-induced or pH-dependent escape of RNA from BDMV has been investigated by 31P NMR spectroscopy and ultracentrifugation. The methods show a transition pH near 6.8 at which the RNA undergoes a structural alteration probably caused by disruption of protein-RNA linkages. Addition of cations or polyamines to BDMV prevents the RNA loss at alkaline pH; the virions become stable to pH values up to 11.5 as observed for TYMV. We suggest that repulsion of the negatively charged phosphate groups of the nucleic acid provides the driving force for RNA release at pH values above the threshold point where protein-RNA interactions are broken. The polyamines effectively counter the phosphate charge in BDMV and thereby prevent RNA loss. Since TYMV is packaged with polyamines and BDMV is not (R. Virudachalam, K. Sitaraman, K. L. Heuss, P. Argos, and J. L. Markley, Virology 130, 360-371, 1983), the different conditions required for RNA escape from the two viruses are explained. Heating of BDMV virions at pH 7.0 to 40 degrees resulted in their partial disruption; the product some intact particles, empty capsids, and RNA fragments with a sedimentation coefficient of 5S.