Effect of oestrogen on the responsiveness of the pituitary gland to LRH: the role of corpora lutea.
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Biomedical subjects
T R Koiter
Publications and source records attributed to T R Koiter.
On the development of pituitary responsiveness to LRH and the characteristics of pre-ovulatory LH-surges in the rat. Effect of oestradiol benzoate.
Administration of oestradiol benzoate (OeB) on the second day of dioestrus of 5-day cyclic rats may advance ovulation by 24 h. The threshold dose of OeB necessary to achieve this effect varies with the time of administration. At 09.00 h, the 50% effective dose (ED-50) of OeB for advancing ovulation was 3.1 microgram; at 17.00 h it was 31 microgram. In the present study OeB was injected at either 09.00 or 17.00 h at doses about 3 times the corresponding ED-50's: 10 and 100 microgram, respectively. Though both regimens of OeB administration resulted in advancement of ovulation, neither had more than a moderate effect on the development of pituitary responsiveness to LRH. In neither group could OeB-induced LH-surges be distinguished from "normal" 4-day rat-LH-surges and both differ from 5-day rat-LH-surges. It is concluded that (1) in the "Everett-model" OeB acts almost exclusively on the central nervous system; (2) the oestrogen-induced surge of LH is an all-or-none effect; and (3) there exists no relationship between the blood oestrogen concentrations and the characteristics of the induced LH-surges.
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LH-secretory responses caused by continuous infusion of LH-RH in pseudopregnant rats.
The LH-secretory response (LH-S.R.), caused by (standard) infusion of LH-RH, was estimated throughout pseudopregnancy (PSP) as well as on dioestrus - 1 and - 2 of the 4-day oestrous cycle. The LH-S.R. was judged according to 3 parameters: (1) mean maximal plasma LH concentration ("height", expressed in ng LH-RP-1/ml plasma), (2) mean area under the curve (AUC, expressed in "area units"), and (3) a composite, dimensionless, parameter: RQ ("response quotient"), defined as height/AUC. This latter parameter informs on the shape of the curve. The LH-S.R.'s on day 1 of PSP and dioestrus-1 were both relatively low (about 350 ng LH-RP-1/ml plasma) and characterized by the same RQ about 12). On days 2, 5, 7 and 9 of PSP the LH-S.R.'s were essentially the same and appeard to have characteristics of the LH-S.R.'s of both PSP-1 and dioestrus-1 (RQ) and dioestrus-2 (height; about 1000 ng LH-RP-1/ml plasma). From day 10 on the LH-S.R.'s became increasingly higher (PSP 11: about 1900 ng LH-RP-1/ml plasma; PSP 12: about 3300 ng LH-RP-1/ml plasma) and steeper (RQ equals about 22). At the end of PSP the spontaneous LH-surges were measured. These appeared to be very high if compared to those which are generated in 4-day cyclic rats (about 5800 ng LH-RP-1/ml plasma). The results indicate that a period of PSP is not simply an ovulatory cycle of which the dioestrous phase is extended by about a week and it is suggested that "active" corpora lutea secrete, next to progesterone, substances which play a key role in the regulation of the secretion of LH in the course of PSP.
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A possible role of corpora lutea with regard to oestrogen-induced changes in pituitary responsiveness to LH-RH.
The effect of oestradiol benzoate (OeB; 3 micrograms sc) on LH-RH-induced LH-secretory responses was investigated in: (1) long-term ovariectomized (OVX) rats; (2) intact (i.e. sham-OVX) and 24 h-OVX persistent oestrous (PO) rats (intact PO rats do not possess corpora lutea); (3) intact and 24 h-OVX cyclic (dioestrous) rats (intact cyclic rats possess "not-activated" corpora lutea), and (4) intact and 24 h-OVX phase-2-pseudopregnant (phase-2-PSP) rats (phase 2 of PSP lasts from day 2 to day 10. Experiments were performed on days 7--8. Intact phase-2-PSP rats possess "activated" corpora lutea). A "positive" effect of OeB was observed in: (1) long-term OVX rats; (2) intact and 24 h-OVX PO rats; (3) 24 h-OVX cyclic rats and (4) 24 h-OVX phase-2-PSP rats. In intact cyclic and phase-2-PSP rats OeB was completely ineffective. From these observations it is concluded that only in the absence of corpora lutea OeB can exert a "positive" effect on LH-RH-induced LH-secretory responses. Ovariectomy alone, however, may have a negative impact on LH-RH-induced LH-secretory responses. This holds for PO- and phase-3-PSP rats (phase 3 of PSP begins once the corpora lutea come to lysis, i.e. on or shortly before day 10, and lasts until the end of PSP), but not for phase-2-PSP rats. In cyclic rats, on the other hand, ovariectomy performed on dioestrus-1 "only" interferes with the normal development of pituitary responsiveness to LH-RH and this can be nullified by OeB. Our observations suggest that (1) relatively long-acting products of corpora lutea "stabilize" (phase-2-PSP rats), c.q. limit the (almost certainly oestrogen-dependent) development of pituitary responsiveness to LH-RH (cyclic and phase-3-PSP rats); (2) in ovariectomized rats the influence of these products vanishes and that (3) this results in a situation in which OeB can become effective. It is also suggested that in the course of the ovulatory cycle and phase 3 of PSP a similar disappearance of corpora luteal products occurs "spontaneously" as a result of the process of luteolysis with as a consequence that the pituitary responsiveness to LH-RH, under the influence of endogenous oestrogens, develops continuously until, on pro-oestrus, an LH-surge occurs. Evidence is presented that the corpora luteal products, postulated in this paper, are not identical to progesterone.
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Leucocyte invasion of the vaginal epithelium in the absence of bacteria in mice.
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Regulation of the bacterial microflora of the vagina in cyclic female rats.
The bacterial microflora was examined in the vagina of cyclic female rats kept under normal laboratory conditions. Large variations occurred during the cycle with high numbers of bacteria (10(5)-10(8) per vagina) during proestrus and estrus and low numbers (10(1)-10(4) per vagina) during the diestrus period. Histological analysis of in situ vaginal tissue and transplanted vaginal tissue revealed an association of high bacterial numbers with the presence of large amounts of cellular debris in the vaginal lumen during the period of epithelial keratinization. Absence of phagocytosis in leucocytes at mestestrus suggested that leucocytes did not play an active role in reduction of bacterial numbers between estrus and metestrus. Accurate measurement of the pH in the vaginal lumen failed to reveal differences which could explain the reduction in bacterial numbers between estrus and metestrus. The cyclic changes in the bacterial population-consisting of species which are normally present in the intestinal flora-- seem to be controlled by cyclic changes in the amounts of cellular debris in the vaginal lumen.
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Effects of food restriction on glucose tolerance, insulin secretion, and islet-cell proliferation in pregnant rats.
Pregnancy is associated with increased glucose-stimulated insulin secretion and increased pancreatic islet-cell proliferation. In the present study it was investigated whether increased food intake, as occurs during pregnancy, is involved in the regulation of these phenomena. From Day 0 of pregnancy, rats received each day the mean amount of food they consumed daily during the estrous cycle prior to conception. This food restriction regime resulted in lower maternal body weight, and in lower fetal weight on Day 20 of gestation, but did not affect fetal survival. Food-restricted rats showed decreased insulin responses to an i.v. glucose challenge on Day 13, and lower islet-cell replication rates on Day 14 of pregnancy than pregnant rats fed ad lib. Plasma lactogenic activity in food-restricted animals was increased on Days 11 and 13; plasma progesterone levels were unchanged, but plasma leptin concentrations declined progressively during food restriction. Glucose tolerance was normal, suggesting that food restriction improved insulin action. On Day 20 of pregnancy, insulin responses were similar in food restricted and ad lib-fed rats; glucose tolerance was still unchanged. It thus seems that the improved insulin action as present on Day 13 had disappeared on Day 20. Also on Day 20, lactogenic activity as well as progesterone concentrations were similar in food-restricted and ad lib-fed rats. It was concluded that increased food intake plays an important role in the stimulation of islet-cell proliferation and insulin secretion, as well as in the diminished insulin action during the second week of rat pregnancy.
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