Kis

MIF gene

sry Coding region element

Regulatory region

Mullerian Inhibiting Factor

Leydig cell

Sertoli cell figure 14-17 Schematic model describing the biological actions of the SRY protein on inducing the expression of the Mullerian inhibiting factor (MIF) and inhibiting the activation of the cytochrome P450 aromatase gene. SRY protein, a transcription factor, binds to the sry element in the regulatory region of the MIS gene and induces the expression of the 140-kDa MIF dimer in fetal Sertoli cells, causing regression of the paramesonephric (Mullerian) ducts. SRY protein binds to the sry element of the P450 aromatase gene and down-regulates its expression in fetal Leydig cells stimulated by hCG/LH, preventing the conversion of testosterone to estradiol. Testosterone is required for the development of the mesonephric (Wolffian) ducts into the male phenotype. Modified with permission from Kierszenbaum, A. L. (1994). "Mammalian spermatogenesis in vivo and in vitro: A partnership of spermatogenic and somatic cell lineages". Endocr. Rev. 15, 116-134.

epididymis, seminal vesicles, and vas deferens (see Figures 14-14 and 14-15).

Interestingly, the gene for the androgen receptor protein, which is present in all androgen-dependent tissues, has been shown to be present on the X chromosome. Thus, an X-linked gene controls the androgen response of somatic cell types by generating the messenger RNA coding for the nuclear cytosol receptor protein.

C. Pregnancy

1. Placental Transfer of Hormones

While the maternal placental unit provides all of the nutrients, electrolytes, water, vitamins, and thermogenic, respiratory, and excretory functions required for fetal growth, an important endocrinological problem has been to elucidate the relative independence-dependence of the fetus from the mother with respect to the plethora of peptide and steroid hormones. Since there is no direct circulatory connection between the maternal placenta and fetal placenta (see Figure 14-3), transfer of hormones cannot occur by "direct" pathways. It has been determined that the placenta is impermeable to all polypeptide and thyroid hormones. However, steroid hormones and the catecholamines epinephrine and norepinephrine are capable of transfer across the placenta. Thus, as described in Figures 14-9 and 14-10, the fetus, mother, and placenta work cooperatively to produce and transfer the required amounts of progesterone and estrogen to the maternal placental unit to maintain pregnancy. Presumably the transfer of the steroid hormone occurs by a simple diffusional process.

2. Fetal Endocrinology

In view of the general lack of hormone transfer to the fetus from the mother, it is clear that the growing fetus must develop its endocrine system in coordination with its own growth and development. It is essential by the time of parturition that all endocrine systems be operative and competent to assume responsibility for their respective domains. However, growth of the

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