Oestrogen-Induced Proteins and Uterine Growth in the Androgenized Female Rat

Abstract

Administration of testosterone propionate (TP) to neonatal female rats induces a syndrome of sterility, characterized by acyclicity and anovulation (Barraclough & Gorski, 1961;Gorski, 1966;Lobi & Gorski, 1969). This study shows the ability of the uterus of androgenized female rats to respond to oestradiol by change in weight and by formation of specific oestrogen-induced proteins (IP) (Barnea & Gorski, 1970).To study the response of the uterus to oestradiol, groups of 15 normal dioestrous and 15 androgenized (1\m=.\25mg TP s.c. on postnatal day 3) adult female rats were hemihysterectomized (ipsilateral ovary removed simultaneously) and the excised uterine tissue was cleaned and weighed. These animals were then injected twice daily with 4 \g=m\g oestradiol benzoate for 5 days. On the 6th day, all animals were killed and the remaining uterine horn was excised, cleaned and weighed. Another group of nine androgenized and ten oestrous females were bilaterally ovariectomized. Six days later, one uterine horn was excised and weighed and oestrogen administered as above.This experiment confirms the findings of Wrenn, Wood & Bitman (1969) that the initial weight of the uterus is similar in normal dioestrous female (NF) and in androgenized female (AF) rats (NF = 113-9± 11-4 (s.e.m.) mg; AF = 114-4 + 4-9). The uterus of the normal female responded to oestradiol treatment by a 62% increase in wet weight (184-7 + 13-6 mg; < 0-001), but that of the AF rats did not (weight = 122-0 ±4-7 mg). In response to ovariectomy, uteri from both NF and AF rats responded by decreases in wet weight to similar levels (NF = 59-3+1-74; AF = 63-9 + 2-1). Administration of oestradiol increased uterine weight in ovari¬ ectomized rats to levels approaching oestrogen-injected, hemihysterectomized rats (NF = 152-83 ± 7-1 ; AF = 119-3 ± 3-7). These results suggest that the uterus from AF rats is tonically maximally stimulated and is less responsive to oestradiol than the normal uterus, although the response to oestrogen after ovariectomy and uterine atrophy is apparently similar.To test the ability of androgenized rats to respond to oestradiol by the formation of IP, we used the double-labelling method exactly as described by Katzenellenbogen & Gorski (1972). One uterus from a 3-day ovariectomized normal or ovariectomized and androgenized female was incubated in 1 ml Eagle's HeLa tissue culture medium. Control uteri were incubated in the absence of steroid and in the presence of 5/¿Ci L-[4,5-14CJleucine (312 mCi/mmol)/ml while experimental tissues were incubated in medium containing 3-7 IO-8 M-oestradiol-17/? and 20/¿Ci L-[3HJleucine (2-0 Ci/mmol)/ml. Three control and three experimental uteri were

Androgenization: Alterations in the Mechanism of Oestrogen Action

“…Our data raise questions concerning the nature of this relationship. We have previously demonstrated that uteri from normal females and androgenized females are dis¬ similar in their growth response to oestrogen (Lobi, Trotta & Brumberger, 1974). Uteri from normal and from androgenized females are similar in weight, atrophy to a similar extent 6 days after ovariectomy, and initially grow at a similar rate as indicated by tissue weights 24 h after oestrogen administration (at this point uteri from androgenized females abruptly cease to grow while uteri from normal females continue to grow, Lobi & Maenza, 1975).…”

Perinatal exposure to androgen excess and the effects on the rat uterine estradiol responsiveness

“…Several studies showed that adult rats neonatally treated with androgens have reduced uterine responsiveness (Wilson et al, ; Petrusz and Flerkó, ; Gerall et al, ; Lobl et al, ; Lobl and Maenza, ) and estradiol binding capacity at adult age (Flerkó and Mess, ; Maurer and Woolley, ; Vértes and King, ; Vértes et al, ). Contrarily, Wrenn et al () showed that female rats exposed to a single dose of TP at 250 µg on PND3 had no significant weight alteration in response to estradiol at adulthood.…”

“…Early postnatal exposure to androgens may lead to adverse reproductive effects in the adulthood as dysfunctional steroidogenesis, irregularity on estrus cycle, and follicular growth impairment (Ongaro et al, ). Besides, in steroid target tissues, the presence of androgens during critical periods of sexual differentiation induces permanent alterations that may affect the responsiveness of these tissues to estrogen (Lobl et al, ; Lobl, ). There are some studies showing that androgen exposure can decrease the uterine response to estrogenic stimulation (Harris and Levine, ; Petrusz and Flerkó, ) and induce changes in the hormone‐induced uterine growth (Lobl and Maenza, ).…”

Altered Sensitivity of Uterus to Progesterone-Estradiol in Rats Treated Neonatally with Androgen and Ovariectomized as Adults

“…However, permanent disruption of normal function is also observed in organs other than the brain in steroid-sterilized rats. Anterior pituitary and uterine tissue are less responsive to estrogen (Hayashi, 1967;Wrenn et al, 1969;Lobl et al, 1974). Unusual reactivity of uterine mucosa is also shown by the metaplasia and hypertrophy of the epithelium following estrogen injections (Takewaki , 1968;Takewaki and Kawashima , 1967 On the 4th day of the 7-day period of progesterone-estradiol injections, endometrium of the right uterine horn of each rat was scratched along the entire length by a needle with a bent point inserted into the uterine lumen via a small incision made near the cervical end of the horn (Takewaki, 1969).…”