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Opposite effects of dihydrotestosterone and estradiol on apoptosis in the anterior pituitary gland from male rats

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Abstract

Hormones locally synthesized in the anterior pituitary gland are involved in regulation of pituitary cell renewal. In the pituitary, testosterone (T) may exert its actions per se or by conversion to dihydrotestosterone (DHT) or 17β-estradiol (E2) by 5α-reductase and aromatase activity, which are expressed in this gland. Previous reports from our laboratory showed that estrogens modulate apoptosis of lactotropes and somatotropes from female rats. Now, we examined the in vitro and in vivo effects of gonadal steroids on apoptosis of anterior pituitary cells from adult male rats. T in vitro did not modify apoptosis in anterior pituitary cells from gonadectomized (GNX) male rats. DHT, a non-aromatizable androgen, exerted direct antiapoptotic action on total anterior pituitary cells and folliculo-stellate cells, but not on lactotropes, somatotropes, or gonadotropes. On the contrary, E2 exerted a rapid apoptotic effect on total cells as well as on lactotropes and somatotropes. Incubation of anterior pituitary cells with T in presence of Finasteride, an inhibitor of 5α-reductase, increased the percentage of TUNEL-positive cells. In vivo administration of DHT to GNX rats reduced apoptosis in the anterior pituitary whereas E2 exerted proapoptotic action and reduced cells in G2/M-phase of the cell cycle. In summary, our results indicate that DHT and E2 have opposite effects on apoptosis in the anterior pituitary gland suggesting that local metabolization of T to these steroids could be involved in pituitary cell turnover in males. Changes in expression and/or activity of 5α-reductase and aromatase may play a role in the development of anterior pituitary tumors.

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Acknowledgments

We would like to thank Miss Mercedes Imsen for her kind help with animal care and handling. This work was supported by grants from the Agencia Nacional de Investigaciones Científicas y Tecnológicas, National Research Council (CONICET) and the University of Buenos Aires, Argentina.

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  1. Instituto de Investigaciones Biomédicas (UBA-CONICET), Paraguay 2155, C1121ABG, Buenos Aires, Argentina

    María Laura Magri, María Florencia Gottardo, Sandra Zárate, Guadalupe Eijo, Jimena Ferraris, Gabriela Jaita, Mariela Moreno Ayala, Marianela Candolfi, Daniel Pisera & Adriana Seilicovich

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  1. María Laura Magri
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  2. María Florencia Gottardo
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  3. Sandra Zárate
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  4. Guadalupe Eijo
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Correspondence to Adriana Seilicovich.

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Magri, M.L., Gottardo, M.F., Zárate, S. et al. Opposite effects of dihydrotestosterone and estradiol on apoptosis in the anterior pituitary gland from male rats. Endocrine 51, 506–516 (2016). https://doi.org/10.1007/s12020-015-0719-2

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