Sexual dimorphism in the effect of concomitant progesterone administration on changes caused by long-term estrogen treatment in pituitary hormone immunoreactivities of rats

Abstract

Background: Since in clinical practice long-term estrogen (E) treatment is frequently applied, our aim was to study the effect of concomitant progesterone (P) administration on changes caused by long-term estrogen treatment in the secretion of LH, FSH, PRL and GH.

Material/methods: Diethylstilbestrol (DES), P or both in silastic capsules were implanted under the skin of prepubertal Sprague-Dawley male and female rats. Animals survived for two or five months. We have also studied whether the changed hormone secretion caused by DES can return to normal level 1 or 2 months after removing DES capsule.

Results: 1.) The males more rapidly responded than females with decreasing basal LH release upon treatments. The basal FSH release was decreased only in males. The effect of DES persisted in males; however, in females basal LH and FSH levels were upregulated after removal of DES capsule. 2.) The basal GH levels were low in each group. The body weight and length were depressed by DES in both genders and P little blunted this effect. The body weight and length in males remained low after removal of DES capsule, in females it was nearly similar to intact rats. 3.) There was no sexual dimorphism in the effect of steroids on PRL secretion. In both genders DES extremely enhanced the PRL levels, P prevented the effect of DES. PRL levels returned to intact value after removal of DES influence. 4.) Removal of DES capsule reversed the changes in the immunohistochemical appearance of hormone immunoreactivities.

Conclusions: There was sexual dimorphism in the change of basal gonadotropic hormone and GH secretion but not of PRL upon DES and DES+P treatments. P was basically protective and this role may be mediated by P receptors locally in the pituitary gland.

Figure 1

LH plasma levels in various experimental groups. (A) shows LH levels in female rats with two-month survival after the implantation of capsules, (B) with five month survival, and (C) shows LH in the animals two months after the implantation of DES capsule, and one and two months after the removal of DES capsule. (D–F) show LH data in male rats of similar experimental groups as in females. Numbers in the columns or above them indicate the number of animals included in the given group. Abbreviations: DES – diethylstilbestrol; ecap – empty capsule; P – progesterone.

Figure 2

FSH plasma levels in various experimental groups. (A) shows FSH levels in female rats with two-month survival after the implantation of capsules, (B) with five-month survival, and (C) shows FSH in the animals two months after the implantation of DES capsule, and one and two months after the removal of DES capsule. (D–F) show FSH data in male rats of similar experimental groups as in females. Numbers in the columns or above them indicate the number of animals included in the given group. Abbreviations: DES – diethylstilbestrol; ecap – empty capsule; P – progesterone.

Figure 3

PRL plasma levels in various experimental groups. (A) shows PRL levels in female rats with two-month survival after the implantation of capsules, (B) with five-month survival, and (C) shows PRL in the animals two months after the implantation of DES capsule, and one and two months after the removal of DES capsule. (D–F) show PRL data in male rats of similar experimental groups as in females. Numbers in the columns or above them indicate the number of animals included in the given group. Abbreviations: DES – diethylstilbestrol; ecap – empty capsule; P – progesterone.

Figure 4

GH plasma levels in various experimental groups. (A) shows GH levels in female rats with two-month survival after the implantation of capsules, (B) with five-month survival, and (C) shows GH in the animals two months after the implantation of DES capsule, and one and two months after the removal of DES capsule. (D–F) show GH data in male rats of similar experimental groups as in females. Numbers in the columns or above them indicate the number of animals included in the given group. Abbreviations: DES – diethylstilbestrol; ecap – empty capsule; P – progesterone.

Figure 5

Microphotographs showing anterior pituitary sections stained for LH, FSH, PRL and GH immunoreactivities using indirect immunofluorescence method. (A–H) derived from intact rats, (I–X) from different experimental groups. In the gonadotropic zone of both female and male rats the density of LH and FSH cells is higher than in the other part of the anterior lobe indicated by asterisk (A–D). PRL cells are evenly distributed in intact rats (E,F). GH cells are completely missing from the gonadotropic zone (indicated by arrow) of both female (G) and male (H) rats, anywhere else they are also evenly distributed. In rats with 2-month survival after DES implantation the number of LH cells much lower than in intact rats (I). The decrease of LH cells is more pronounced 5 months after implantation (J). Implantation of P together with DES prevented the serious decrease in the number of LH cells (K,L). DES implantation for 2 months increased the size and number of PRL cells (M). (N) shows cup shaped PRL cells in an intact male rat, (O) shows hypertrophized ovoid and rounded PRL cells in a DES treated rat with 2-month survival, (P) shows medium sized PRL cells from a DES+P treated male rat. DES implantation in animals with 5-month survival induced appearance of adenomatous areas composed of PRL cells. One of these prolactinomas is shown in (Q). The histological appearance of PRL immunostaining is very similar to intact rats. Concomitant P implantation with DES for 5 months prevented the hypertrophy of PRL cells (R). (S) shows GH staining in a male rat with 5-month DES influence. GH cells are missing from a region resembling prolactinoma (§). Double labeling (T) for GH and PRL shows a prolactinoma (outlined by arrows). GH cells are missing from this adenomatous region. (U) shows GH staining in a male rat with DES+P implantation. GH cells show similar distribution than in intact rats; however, they are also present in the gonadotropic zone. Removal of DES capsule restored the appearance of immunostaining for LH (V), PRL (W) and GH (X). Abbreviations: 2 m – 2-month survival; 5 m – 5-month survival; rem 1 m – 1-month survival after removal of DES capsule; rem 2 m – 2-month survival after removal of DES capsule. Scale: 750 μm in (A–M) and (Q–X), and 100 μm in (N–P).