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We developed an ELISA system for the detection of human anti-ovarian antibodies. Bovine corpora lutea were extracted in PBS (pH 7.2) and fractionated by ultracentrifugation. Both the soluble fraction obtained after 80,000 g (S80) and the Tritonextracted membrane fraction (ST288) were used as antigens. Additionally, the luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor was isolated by affinity chromatography (wheat germ agglutinin and LH-Sepharose) and also used as an antigen.In 7 of 14 patients with primary sterility and endometriosis a positive reaction was observed. Similarly, 6 of 16 patients with secondary sterility and endometriosis were also positive. Patients being stimulated for in vitro fertilization and presenting either primary or secondary sterility were positive in 5 of 22 and 6 of 16 cases, respectively. In the S80 test 41 of 60 sera presented IgG2 antibodies, whereas in the ST288 test 38 of 60 belonged to the IgG, subclass. Kappa and lambda chains were equally distributed.Some patients could recognize the unoccupied LH/hCG receptor as an antigen, while others recognized only the complex formed by the hormone plus the hormone receptor.The S80 and ST288 antigens were isolated by affinity chromatography. Gel permeation of the purified antigens revealed in each case the presence of an antigen complex. The apparent molecular weight was between 2,000 and 36,000 D. Cross-reactivity studies using affinity-purified antibodies demonstrated an antigenic relationship of the membrane, soluble, and extractable fractions. NAc-(beta-1 -4)-D-glucosaminide and -D-galactopyranoside were the main terminal glycosides.

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In a prospective study 911 patients were treated over a period of 5 years (M = 2.2) or a total of 2007 treatment years with estriol succinate oral (Synapause, 2-12 mg per day). The treatment was very effective in the removal of all typical climacteric complaints and of the atrophic genital changes caused by estrogen deficiency. Subjective side effects were seldom seen and without practical importance for the treatment. Objective, grave side effects were only few: one superficial phlebo-thrombosis, 2 cases of thrombophlebitis, one carcinoma in situ of the portio vaginalis uteri and 2 mammary cancers were seen. The carcinoma had probably no causal relationship to the treatment. Embolies, myocardial infarctions, cerebrovascular and liver-gall bladder complications did not occur during treatment. The rate of uterine bleedings was low. The incidence of all complications was not increased by estriol succinate; but was even lower than expected. Endometrial and ovarian cancers were not seen. Estriol succinate is accordingly a very effective and well tolerated preparation against climacteric complaints, exerting no significant side effects. It is remarkable that it does not proliferate the endometrium when given in one dose a day. Estriol succinate can therefore be characterized as the estrogen to be favoured for the treatment of postclimacteric women, who do not want to have uterine bleedings any longer.(ABSTRACT TRUNCATED AT 250 WORDS)

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While numerous investigations have determined characteristics of episodic luteinizing hormone (LH) secretion in women, any diurnal LH rhythmicities during eugonadal and hypogonadal states have not been accurately addressed. Accordingly, blood was sampled at 15-min intervals for 24 h in 45 normally cycling women (16 early follicular (EFP), 14 late follicular (LFP), 15 mid-luteal phase (MLP) women) and in eight postmenopausal women (PMW). Pulse attributes (amplitudes, interpulse intervals) determined in the LH secretory profiles were fitted to cosinor functions to assess diurnal variabilities. In both eugonadal women and PMW, significant (p less than 0.05 or less) diurnal excursions were observed in mean LH levels, with maximal acrophase amplitudes occurring in the EFP and MLP. While these 24-h swings peaked at comparable times (11.00-17.00) during the menstrual cycles, a significant (p less than 0.001) shift in acrophase times to early morning hours (05.30) was noted for PMW. Significant (p less than 0.05 or less) 24-h periodicities were also found for the LH pulse amplitudes. LH pulses were of greater magnitudes during night hours in both cycling women and PMW. A slowing of LH pulses (p less than 0.05 or less) was noted during sleep in EFP and, distinctly, in MLP women. These observations demonstrate diurnal variations in LH secretion and its pulsatile attributes in eugonadal women. Differences in time course and magnitude of these diurnal excursions may be explained by variations in the sex steroid environments. In turn, steroids may modulate other neuroendocrine determinants regulating central time-keepers.

The urinary excretion of the individual 3β-hydroxy-Δ5 steroids together with cortisol and the chromatographic bands of material containing its tetrahydrometabolites, have been studied in early infancy before and after stimulation by exogenous corticotrophin (ACTH). The average increase in the excretion of the Δ5 steroids after stimulation is relatively small (less than 185%) compared with the increase in cortisol and its metabolites (greater than 600%) and it is suggested that ACTH stimulation cannot be solely responsible for the formation of the considerable quantities of Δ5 steroids in early infancy and the high Δ5 steroid/cortisol production ratio in utero.

The placental oestrogen precursors [4-14C]dehydroepiandrosterone (DHA) and [4-14C]androstenedione (AD) were incubated with microsomal fractions of human placentas from normal and pathological pregnancies at different stages of gestation, in order to evaluate the rate of conversion of the substrates to oestrogens. In placentas from normal pregnancies the capability to convert C19-steroids (DHA and AD) to C18-steroids (oestrone and oestradiol017β) increased with the age of gestation. The placenta at term metabolizes [4-14C]DHA and [4-14C]AD into oestrogens (oestrone and oestradiol-17β) with a four times greater aromatisation rate than the placenta at midpregnancy. The concentration of protein in the placental microsomal fraction also increased with the age of gestation. In our aromatisation studies it was found that the conversion rate of DHA and AD to oestrogens (oestrone and oestradiol-17β) by placental microsomes was significantly lowered in toxaemic and diabetic placentas and in placentas of postmaturity cases as compared to normal placentas at term. The relationship between placental insufficiency and a lowered capacity of Δ5-Δ4-isomerase, 3β-hydroxysteriod-dehydrogenase and the aromatizing enzyme systems is discussed with regard to the main causes of a low oestriol excretion and a low aromatisation rate of injected DHA-S in pathological pregnancies. Finally it is shown, that the parameters of the hormonal investigations correlate with the degree of pathological microscopic alterations of the placentas.