The fetal endocrine system is one of the first systems to develop during prenatal development of a human individual. The endocrine system arises from all three embryonic germ layers. The endocrine glands that produce the steroid hormones, such as the gonads and adrenal cortex, arise from the mesoderm. In contrast, endocrine glands that arise from the endoderm and ectoderm produce the amine, peptide, and protein hormones.
Adrenal glands
The fetal Adrenal Cortex can be identified within four weeks of pregnancy. The adrenal cortex originates from the thickening of the intermediate Mesoderm. At five to six weeks of gestation, the Mesonephros differentiates into a tissue known as the gonadal ridge. The gonadal ridge produces the Steroidogenic cells for both the gonads and the adrenal cortex. The adrenal medulla is derived from Ectodermal cells. Cells that will become adrenal tissue move Retroperitoneally to the upper portion of the Mesonephros. At seven weeks of gestation, the adrenal cells are joined by sympathetic cells that originate from the Neural Crest to form the Adrenal Medulla. At the end of the eighth week, the adrenal glands have been encapsulated and have formed a distinct organ above the developing kidneys. At birth, the adrenal glands weight approximately eight to nine grams (twice that of the adult adrenal glands) and are 0.5% of the total body weight. At 25 weeks, the adult adrenal cortex zone develops and is responsible for the primary synthesis of steroids during the early postnatal weeks.
Thyroid gland
The Thyroid gland develops from two different clusterings of embryonic cells. One part is from the thickening of the Pharyngeal floor, which serves as the precursor of the Thyroxine (T4) producing Follicular cells. The other part is from the Caudal extensions of the fourth Pharyngobranchial pouches which results in the Parafollicular Calcitonin-secreting cells. These two structures are apparent by 16 to 17 days of gestation. Around the 24th day of pregnancy, the Foramen Cecum, a thin, flask-like Diverticulum of the median Anlage develops. At approximately 24 to 32 days of gestation the median anlage develops into a bilobed structure. By 50 days of gestation, the medial and Lateral Anlage have fused together. At 12 weeks of gestation, the Fetal Thyroid is capable of storing iodine for the production of TRH, TSH, and free thyroid hormone. At 20 weeks, the Fetus is able to implement feedback mechanisms for the production of thyroid hormones. During fetal development, T4 is the major thyroid hormone being produced while Triiodothyronine (T3) and its inactive derivative, reverse T3, are not detected until the third trimester.
Parathyroid glands
Once the embryo reaches four weeks of gestation, the parathyroid glands begins to develop. The human embryo forms five sets of endoderm-lined pharyngeal pouches. The third and fourth pouch are responsible for developing into the inferior and superior parathyroid glands, respectively. The third pharyngeal pouch encounters the developing thyroid gland and they migrate down to the lower poles of the thyroid lobes. The fourth pharyngeal pouch later encounters the developing thyroid gland and migrates to the upper poles of the thyroid lobes. At 14 weeks of gestation, the parathyroid glands begin to enlarge from 0.1 mm in diameter to approximately 1 – 2 mm at birth. The developing parathyroid glands are physiologically functional beginning in the second trimester.
Studies in mice have shown that interfering with the HOX15 gene can cause parathyroid gland aplasia, which suggests the gene plays an important role in the development of the parathyroid gland. The genes, TBX1, CRKL, GATA3, GCM2, and SOX3 have also been shown to play a crucial role in the formation of the parathyroid gland. Mutations in TBX1 and CRKL genes are correlated with DiGeorge syndrome, while mutations in GATA3 have also resulted in a DiGeorge-like syndrome. Malformations in the GCM2 gene have resulted in hypoparathyroidism. Studies on SOX3 gene mutations have demonstrated that it plays a role in parathyroid development. These mutations also lead to varying degrees of hypopituitarism.